Circadian modulation of GABA-mediated cortical inhibition

Circadian rhythms exert powerful influence on various aspects of human physiology and behavior. Here, we tested changes of human cerebral cortex excitability over the course of the day with transcranial magnetic stimulation (TMS). At different times of the day, intracortical and corticospinal excitability of the primary motor cortex (M1) was evaluated in 15 healthy subjects by TMS of left M1. While motor thresholds, short-interval intracortical inhibition and facilitation and input/output curves remained unchanged, we found that a specific form of γ-aminobutyric acid (GABA)-mediated intracortical inhibition, revealed by long-interval intracortical inhibition and cortical silent periods, progressively decreased during the course of the day. Additional experiments demonstrated that morning inhibition persisted irrespective of previous sleep or sleep deprivation. Corticotropin-releasing hormone (CRH) infusions in the evening lead to morning cortisol levels but did not restore levels of morning inhibition, whereas suppression of endogenous CRH release by repeated oral dexamethasone intake over 24 h prevented morning inhibition. The findings suggest a specific modulation of GABAergic motor cortex inhibition within the circadian cycle, possibly linked to the CRH system, and may indicate a neurobiological basis for variable neuroplasticity over the course of the day.     

Three-dimensional anisotropy contrast magnetic resonance axonography to predict the prognosis for motor function in patients suffering from stroke.

OBJECT: The purpose of this study was to assess how early wallerian degeneration in the corticospinal tracts of patients who had suffered from stroke was detected using three-dimensional anisotropy contrast (3D-AC) magnetic resonance (MR) axonography and to explore the possibility of predicting the prognosis for motor function in these patients. METHODS: Ten healthy volunteers and 16 stroke patients with hemiparesis were studied using MR images including 3D-AC MR axonography images obtained using a 1.5-tesla MR imaging system. The axonography was performed using an echoplanar imaging method. All patients underwent MR studies 2, 3, and 10 weeks after stroke onset. To detect wallerian degeneration, the diffusion anisotropy in the corticospinal tracts at the level of the upper pons was evaluated on axial images. These MR findings were compared with the patients' motor functions, which were classified according to the Brunnstrom criteria 12 weeks after the onset of stroke. In all patients with poor recovery (Brunnstrom Stages I-IV), wallerian degeneration, which was demonstrated as a reduction in diffusion anisotropy on axonography images, could be observed in the corticospinal tracts; this degeneration was not found in patients with good recovery (Stages V and VI). Axonography could be used to detect degeneration between 2 and 3 weeks after stroke onset. On conventional T2-weighted MR images, hyperintense areas indicating wallerian degeneration were not detected until 10 weeks after stroke onset. CONCLUSIONS: With the aid of 3D-AC MR axonography, wallerian degeneration can be detected in the corticospinal tracts during the early stage of stroke (2-3 weeks after onset), much earlier than it can be detected using T2-weighted MR imaging. The procedure of 3D-AC MR axonography may be useful in predicting motor function prognosis in stroke patients.     

Athletes after anterior cruciate ligament reconstruction demonstrate asymmetric intracortical facilitation early after surgery

Quadriceps dysfunction persists after anterior cruciate ligament reconstruction (ACLR), yet the etiology remains elusive. Inhibitory and facilitatory intracortical networks (ie, intracortical excitability) may be involved in quadriceps dysfunction, yet the investigation of these networks early after ACLR is sparse. The purposes of this study were to examine (a) changes in intracortical excitability in athletes after ACLR compared to uninjured athletes during the course of postoperative rehabilitation, (b) the association between intracortical excitability and quadriceps strength in athletes after ACLR. Eighteen level I/II athletes after ACLR between the ages of 18 to 30 years and eighteen healthy sex, age, and activity matched athletes were tested at three‐time points: (a) 2 weeks after surgery, (b) achievement of a “quiet knee” defined as full range of motion and minimal effusion, (c) return to running time point defined as achievement of a quadriceps index ≥80% and at least 12 weeks post‐ACLR. Short‐interval intracortical inhibition (SICI) and intracortical facilitation (ICF), measured via transcranial magnetic stimulation and isometric quadriceps strength were examined bilaterally at each time point. There was a significant group × limb interaction (P = .017) for ICF. The ACLR group demonstrated asymmetric ICF (greater in the nonsurgical limb) compared to controls and a significant relationship between SICI and quadriceps strength of the surgical limb at the quiet knee time point (P = .018). ACLR individuals demonstrate differential effects on ICF between limbs. Also, SICI is associated with isometric quadriceps strength after ACLR, suggesting increased inhibition of the motor cortex may contribute to impaired quadriceps strength following ACLR.     

Cortical excitability changes in patients with sleep-wake disturbances after traumatic brain injury

Although chronic sleepiness is common after head trauma, the cause remains unclear. Transcranial magnetic stimulation (TMS) represents a useful complementary approach in the study of sleep pathophysiology. We aimed to determine in this study whether post-traumatic sleep-wake disturbances (SWD) are associated with changes in excitability of the cerebral cortex. TMS was performed 3 months after mild to moderate traumatic brain injury (TBI) in 11 patients with subjective excessive daytime sleepiness (EDS; defined by the Epworth Sleepiness Scale ≥10), 12 patients with objective EDS (as defined by mean sleep latency <5 on multiple sleep latency tests), 11 patients with fatigue (defined by daytime tiredness without signs of subjective or objective EDS), 10 patients with post-traumatic hypersomnia "sensu strictu," and 14 control subjects. Measures of cortical excitability included central motor conduction time, resting motor threshold (RMT), short-latency intracortical inhibition (SICI), and intracortical facilitation to paired-TMS. RMT was higher and SICI was more pronounced in the patients with objective EDS than in the control subjects. In the other patients all TMS parameters did not differ significantly from the controls. Similarly to that reported in patients with narcolepsy, the cortical hypoexcitability may reflect the deficiency of the excitatory hypocretin/orexin-neurotransmitter system. These observations may provide new insights into the causes of chronic sleepiness in patients with TBI. A better understanding of the pathophysiology of post-traumatic SWD may also lead to better therapeutic strategies in these patients.     

Corticospinal excitability in patients with chronic low back pain

OBJECTIVE: This study was designed to investigate corticospinal excitability of lumbar muscles using transcranial magnetic stimulation (TMS) in patients with chronic low back pain and correlate this with self-rated measures of disability and pain. METHODS: Twenty-four patients with chronic low back pain and 11 healthy control subjects were used in this study. TMS was delivered through an angled double-cone coil, with its cross-over on the vertex and a posterior-to-anterior current flow in the brain. Electromyographic (EMG) recordings were made from erector spinae (ES) muscles at the fourth lumbar level. Motor cortical excitability was assessed using motor threshold (MTh) for motor evoked potentials (MEPs) and threshold for silent period (SP) during facilitation of the back muscles. Latency, duration, and area of MEPs and SPs were also measured. RESULTS: The latency, duration, and size of MEPs and SPs did not differ between the left and right ES muscles in either the patients or the control subjects and also did not differ between the patients and the control subjects. However, there was a significantly higher MTh and threshold for the SP in the patients as compared with the control subjects; the full significance of this requires further investigation. Interestingly, there was a positive correlation between the self-rated measure of disability (the Oswestry Disability Index score) and both the MTh and the threshold for the SP in the patients. There was also a positive correlation between the self-rated index of back pain and the threshold for the SP in the patients. This finding of an association between clinical and neurophysiologic measures reinforces the need for further research to establish the clinical relevance of these rises in MTh and SP threshold. CONCLUSIONS: In summary, this study has revealed that corticospinal excitability, driving ES muscles close to the site of pain, is lowered in patients with chronic low back pain.     

Involuntary contralateral upper extremity muscle activation pattern during unilateral pinch grip following stroke

Study designRepeated measures design.IntroductionMirror activity refers to emergence of motion not only in the intended, but also in the contralateral limb.PurposeTo characterize post-stroke mirror activities across multiple muscles during unilateral pinch.MethodsChronic stroke survivors performed unilateral pinch grip using the paretic and nonparetic hand, while four muscles' EMGs were recorded for both hands.ResultsDuring the paretic hand grip, the relaxed nonparetic hand showed mirror activity that was more pronounced for the intrinsic (FDI and thenar eminence) than extrinsic muscles (FDS and EDC). During the nonparetic hand grip, mirror activity in the paretic hand was suppressed for the intrinsic than extrinsic muscles.ConclusionChronic stroke survivors' relaxed hand did not mirror the task hand's muscle activation pattern, but displayed altered muscle activation patterns depending on muscles and sides, possibly mediated by disturbed interhemispheric inhibition and relative reliance on corticospinal tracts among muscles.Level of evidenceN/A.     

Imagery-induced cortical excitability changes in stroke: a transcranial magnetic stimulation study

Focal transcranial magnetic stimulation (TMS) was employed in a population of hemiparetic stroke patients in a post-acute stage to map out the abductor digiti minimi (ADM) muscle cortical representation of the affected (AH) and unaffected (UH) hemisphere at rest, during motor imagery and during voluntary contraction. Imagery induced an enhancement of the ADM map area and volume in both hemispheres in a way which partly corrected the abnormal asymmetry between AH and UH motor output seen in rest condition. The voluntary contraction was the task provoking maximal facilitation in the UH, whereas a similar degree of facilitation was obtained during voluntary contraction and motor imagery in the AH. We argued that motor imagery could induce a pronounced motor output enhancement in the hemisphere affected by stroke. Further, we demonstrated that imagery-induced excitability changes were specific for the muscle 'prime mover' for the imagined movement, while no differences were observed with respect to the stroke lesion locations. Present findings demonstrated that motor imagery significantly enhanced the cortical excitability of the hemisphere affected by stroke in a post-acute stage. Further studies are needed to correlate these cortical excitability changes with short-term plasticity therefore prompting motor imagery as a 'cortical reservoir' in post-stroke motor rehabilitation.     

No difference observed in short-interval intracortical inhibition in older burn-injury survivors compared to non-injured older adults: A pilot study

ObjectiveThe study aimed to investigate short-interval intracortical inhibition (SICI) in burns survivors and non-injured controls, and establish whether paired-pulse transcranial magnetic stimulation (TMS) is a sensitive tool to investigate SICI after burn-injury.MethodsBurn survivors underwent experimental assessments at 6- and 12-weeks after injury, and control participants underwent two equivalent sessions 6 weeks apart. Single-pulse transcranial magnetic stimulation (TMS) was used to record motor-evoked potentials (MEPs) from a hand muscle and paired-pulse TMS was used to measure SICI. Functional measures were obtained for comparison at 12-weeks after injury.ResultsThere was no significant difference in SICI between burns survivors and non-injured controls at either 6- or 12-weeks after burn injury. There was no evidence of correlations between SICI and functional outcome measures in burns survivors.ConclusionsThese results show that paired-pulse TMS is a useful method for investigating cortical inhibition following burn injury, and that SICI circuits in the primary motor cortex are not affected by minor burn injury. This study presents details for definitive future studies of primary motor cortex function after minor burn injury.     

The influence of hand posture on corticospinal excitability during motor imagery: a transcranial magnetic stimulation study

In order to study the interaction between proprioceptive information and motor imagery, we herein investigate how compatible and incompatible postural signals influence corticospinal excitability during the mental simulation of hand movements. Subjects were asked to imagine themselves joining the tips of the thumb and the little finger while they maintained one of the two following hand postures: posture A (PA, compatible), little finger, index and thumb extended, the remaining fingers flexed; or posture B (PB, incompatible), index and thumb extended, other fingers flexed. All subjects rated the imagined finger opposition movements as easier to perform when the hand was kept in PA than in PB (P < 0.01) and the correlation between the duration of motor imagery and movement execution was also higher for PA than PB (P < 0.01). For each posture, motor evoked potentials (MEPs) elicited by focal transcranial magnetic stimulation (TMS) of the left motor cortex were recorded from the right opponens pollicis muscle during both motor imagery (MI) and rest (R) conditions. MEP area varied according to the hand posture: PA induced a higher increase in corticospinal excitability, when compared with PB. These results indicate that the actual limb posture affects the process of motor imagery. The source of this postural modulation effect is discussed.     

Contralesional Hemisphere Control of the Proximal Paretic Upper Limb following Stroke

Cathodal transcranial direct current stimulation (c-tDCS) can reduce excitability of neurons in primary motor cortex (M1) and may facilitate motor recovery after stroke. However, little is known about the neurophysiological effects of tDCS on proximal upper limb function. We hypothesized that suppression of contralesional M1 (cM1) excitability would produce neurophysiological effects that depended on the severity of upper limb impairment. Twelve patients with varying upper limb impairment after subcortical stroke were assessed on clinical scales of upper limb spasticity, impairment, and function. Magnetic resonance imaging was used to determine lesion size and fractional anisotropy (FA) within the posterior limbs of the internal capsules indicative of corticospinal tract integrity. Excitability within paretic M1 biceps brachii representation was determined from motor-evoked potentials during selective isometric tasks, after cM1 sham stimulation and after c-tDCS. These neurophysiological data indicate that c-tDCS improved selective proximal upper limb control for mildly impaired patients and worsened it for moderate to severely impaired patients. The direction of the neurophysiological after effects of c-tDCS was strongly related to upper limb spasticity, impairment, function, and FA asymmetry between the posterior limbs of the internal capsules. These results indicate systematic variation of cM1 for proximal upper limb control after stroke and that suppression of cM1 excitability is not a "one size fits all" approach.     

Transcranial magnetic stimulation in brain injury

Objectives

Transcranial magnetic stimulations (TMS) have been used for many years as a diagnostic tool to explore changes in cortical excitability, and more recently as a tool for therapeutic neuromodulation. We are interested in their applications following brain injury: stroke, traumatic and anoxic brain injury.

Data synthesis

Following brain injury, there is decreased cortical excitability and changes in interhemispheric interactions depending on the type, the severity, and the time-lapse between the injury and the treatment implemented. rTMS (repetitive TMS) is a therapeutic neuromodulation tool which restores the interhemispheric interactions following stroke by inhibiting the healthy cortex with frequencies ≤ 1 Hz, or by exciting the lesioned cortex with frequencies between 3 and 50 Hz. Results in motor recovery are promising and those in improving aphasia or visuospatial neglect are also encouraging. Finally, the use of TMS is mainly limited by the risk of seizure, and is therefore contraindicated for many patients.

Conclusion

TMS is a useful non-invasive brain stimulation tool to diagnose the effects of brain injury, to study the mechanisms of recovery and a non-invasive neuromodulation promising tool to influence the post-lesional recovery.     

Kinematically specific interhemispheric inhibition operating in the process of generation of a voluntary movement

Unilateral hand movements are accompanied by a transient decrease in corticospinal (CS) excitability of muscles in the opposite hand. However, the rules that govern this phenomenon are not completely understood. We measured the amplitude of motor evoked potentials (MEP) in the left first dorsal interosseus (FDI) elicited by transcranial magnetic stimulation (TMS) of the primary motor cortex in order to assess CS excitability changes that preceded eight possible combinations of unilateral and bilateral index finger movements with different right hand positions. Left FDI MEP amplitude (MEP(Left FDI)) increased when this muscle acted as an agonist and tended to decrease when it was an antagonist. Additionally, MEP(Left FDI) decreased substantially before right index finger abduction (a movement mediated by the right FDI) when both hands were lying flat (a movement mirroring left index finger abduction) but not when the right hand was turned at 90 degrees or flat with the palm up. Therefore, CS excitability of the resting FDI was differentially modulated depending on the direction of the opposite index finger movement, regardless of muscles engaged in the task. These results indicate that inhibitory interactions preceding unilateral finger movements are determined by movement kinematics possibly to counteract the default production of mirror motions.     

Stroke survivors talk while doing: Development of a therapeutic framework for continued rehabilitation of hand function post stroke

Study designQualitative study to identify themes and explore mechanisms underlying recovery of hand function post stroke for individuals discharged from rehabilitation services.Purpose of the studyPost-stroke hemiparesis frequently results in persistent hand dysfunction; the mechanisms of functional recovery are however poorly understood. We assessed the perspectives of community-dwelling individuals with chronic stroke on their hand function limitations and recovery to explore the feasibility of developing a theoretical framework for understanding the process of continued post-stroke recovery.MethodsEight subjects with chronic post-stroke hemiparesis were interviewed and videotaped while they performed a battery of 20 upper limb tasks. Qualitative analysis consisted of two investigators independently reviewing the videotapes and reading the transcribed conversations, identifying significant issues and then comparing their observations to determine common themes and develop emerging concepts.ResultsFour core themes pertaining to impairment and recovery of task-specific ability emerged: 1) spasticity can be overcome actively through task-specific attempts to use the affected arm and hand; 2) use of the affected arm can be facilitated by adopting positions that reduce the effect of gravity on the arm or enable gravity to act as a natural assist in the movement; 3) task-specific skill can be attained by repeatedly attempting specific component movements of tasks in the context of a variety of different tasks; and 4) frustration impedes task performance but a mental state of ‘detached focus’ can improve the motivation to use the affected arm.ConclusionsThese themes suggest a therapeutic framework for continued upper limb rehabilitation in patients' own environment to maximize functional recovery in individuals long after their stroke, and generate hypotheses which may lead to the development of new therapeutic protocols.Level of evidenceNA     

Major life events as risk factors for post-stroke depression

Depression is a significant sequela of stroke which contributes to increased morbidity and mortality in stroke survivors. Psychosocial stressors, such as major life events, pose risk factors for developing depression in non-stroke populations. This study evaluated major life events as a risk factor for developing post-stroke depression (PSD) during the first year post-stroke. One hundred and eleven patients who completed the Center for Epidemiological Studies-Depression Scale at four time periods during the first year post-stroke were assessed for PSD and asked if they had experienced a major life event in the prior 6 months (other than the stroke). The subjects completed the evaluations acutely (7-10 days), and at 3, 6, and 12 months post-stroke. At 6 months post-stroke patients were significantly more likely to be depressed if they had a major life event in the prior 6 months (other than the stroke) than if they had not, chi 2 (df = 1) = 4.83, p < 0.028, relative risk = 2.31, 95% confidence interval 1.15-4.62. Life events pose significant risks for developing PSD at 6 months post-stroke. Stroke patients need to be asked about these events and treated for PSD.     

Differences in the corticospinal projection from primary motor cortex and supplementary motor area to macaque upper limb motoneurons: an anatomical and electrophysiological study

To further our understanding of the functional roles of different motor cortical areas, we made a quantitative comparison of the density of corticospinal projections from primary motor cortex (M1) and supplementary motor area (SMA) to spinal motor nuclei supplying hand and finger muscles in four macaque monkeys. We also compared the action of corticospinal outputs excited by electrical stimulation of these two areas on upper limb motoneurons recorded in three anaesthetized macaques. The hand representations of SMA and M1 were first identified using structural magnetic resonance imaging scans and intracortical microstimulation. In the anatomical study we then made focal injections of wheatgerm agglutinin- horseradish peroxidase into these representations, which were subsequently confirmed by analysis of retrograde cortical labelling. Densitometric analysis showed that corticospinal projections from M1 were denser and occupied a greater proportion of the hand muscle motor nuclei than did projections from SMA. In caudal Th1 the densest projections from M1 occupied 81% of this motoneuronal area, compared with only 6% from SMA. In the electrophysiological study, bipolar intracortical stimulation of the hand representation of M1 and SMA evoked direct (D) and indirect (I) corticospinal volleys. Volleys elicited by M1 stimulation had larger amplitudes and faster conduction velocities than those evoked from the SMA. Intracellular recordings were made from 84 contralateral upper limb motoneurons. M1 and SMA stimulation evoked markedly different responses in tested motoneurons: EPSPs were larger and more common from M1 (88% of motoneurons) than from SMA (48%). Some motoneurons (16/84) showed evidence of excitatory postsynaptic potentials mediated by monosynaptic action of the D-wave evoked from M1; these early effects were not observed from the SMA. In most motoneurons (74/84) EPSPs had segmental latencies indicating that they were due to monosynaptic action of the I-wave. The results are consistent with cortico-motoneuronal (CM) connections originating from both SMA and M1 converging upon single motoneurons, but those from M1 are far more numerous and exert stronger excitatory effects than from the SMA. Thus although they may function in parallel, the two CM projections probably make different contributions to upper limb motor control.     

Prognostic value of FMRI in recovery of hand function in subcortical stroke patients

The first objective of the study was to determine whether functional magnetic resonance imaging (fMRI) signal was correlated with motor performance at different stages of poststroke recovery. The second objective was to assess the existence of prognostic factors for recovery in early functional MR images. Eight right-handed patients with pure motor deficit secondary to a first lacunar infarct localized on the pyramidal tract were included. This study concerned moderately impaired patients and recovery of handgrip strength and finger-tapping speed. The fMRI task was a calibrated flexion-extension movement. Ten healthy subjects served as a control group. The intensity of the activation in the "classical" motor network (ipsilesional S1M1, ipsilesional ventral premotor cortex [BA 6], contralesional cerebellum) 20 days after stroke was indicative of the performance (positive correlation). The cluster in M1 was posterior and circumscribed to BA 4p. No area was associated with bad performance (negative correlation). No correlation was found 4 and 12 months after stroke. Prognosis factors were evidenced. The higher early the activation in the ipsilesional M1 (BA 4p), S1, and insula, the better the recovery 1 year after stroke. Although the lesions partly deefferented the primary motor cortex, patients who activated the posterior primary motor cortex early had a better recovery of hand function. This suggests that there is benefit in increasing ipsilesional M1 activity shortly after stroke as a rehabilitative approach in mildly impaired patients.     

Intracortical hyperexcitability in humans with a GABAA receptor mutation

A missense mutation of the gamma2 subunit of the gamma-aminobutyric acid A (GABA(A)) receptor has been linked to an inherited human generalized epilepsy. As synaptic inhibition in the human brain is largely mediated by the GABA(A) receptor, we tested the hypothesis that the GABRG2(R43Q) mutation alters cortical excitability. Fourteen subjects affected by the GABRG2(R43Q) mutation (5 males, mean age: 44 +/- 15 years) and 24 controls (11 males, mean age: 38 +/- 11 years) were studied with transcranial magnetic stimulation (TMS). To assess the specificity of the effect of the mutation, 4 additional family members unaffected by the GABRG2(R43Q) mutation (2 males, mean age: 41 +/- 16 years) were included. Subjects affected by the GABRG2(R43Q) mutation demonstrated reduced net short-interval intracortical inhibition and increased intracortical facilitation assessed with paired-pulse stimulation. Subjects with the mutation had similar motor thresholds to controls both at rest and with weak voluntary activation. No significant differences were noted between groups in the cortical silent period. Our findings provide in vivo evidence for increased intracortical excitability in subjects affected by the GABRG2(R43Q) mutation. These findings are also likely to represent an important clue to the mechanisms linking this gene defect and the epilepsy phenotype.     

Alteration of cortical but not spinal inhibitory circuits in idiopathic scoliosis

Background: The pathogenesis of adolescent idiopathic scoliosis (AIS), including the role of brain and spinal inhibitory circuits, is still poorly elucidated. The aim of this study was to identify which central inhibitory mechanisms are involved in the pathogenesis of AIS.Design: A prospective neurophysiological study, using a battery of neurophysiological tests, such as cutaneous (CuSP) and cortical (CoSP) silent periods, motor evoked potentials (MEP) and paired-pulse transcranial magnetic stimulation (ppTMS).Settings: Neurophysiological laboratory.Participants: Sixteen patients with AIS (14 females, median age 14.4) and healthy controls.Outcome measures: MEPs were obtained after transcranial magnetic stimulation (TMS) and recorded from the abductor pollicis muscle (APB). ppTMS was obtained at interval ratios (ISI) of 1, 2, 3, 6, 10, 15 and 20 ms. The cortical silent period (CoSP) was recorded from the APB. The cutaneous silent period (CuSP) was measured after painful stimuli delivered to the thumb while the subjects maintained voluntary contraction of the intrinsic hand muscles. The data were analyzed and compared with those from healthy subjects.Results: The CoSP duration was significantly prolonged in AIS patients. A significantly higher amplitude of ppTMS for ISI was found in all AIS patients, without remarkable left-right side differences. No significant difference in MEP latency or amplitude nor in the CuSP duration was obtained.Conclusion: Our observation demonstrates evidence of central nervous system involvement in adolescent idiopathic scoliosis (AIS). Lower intracortical inhibition, higher motor cortex excitability, and preserved spinal inhibitory circuits are the main findings of this study. A possible explanation of these changes could be attributed to impaired sensorimotor integration predominantly at the cortical level.     

The biphasic nature of renal functional recovery following relief of chronic obstructive uropathy

Twenty-one patients with chronic obstructive uropathy due to high pressure chronic retention of urine underwent renal functional assessment both during the period of obstruction and repeatedly up to 3 months following its relief. Glomerular filtration rate (GFR) was determined using clearance of 99mTc-DTPA and iohexol. Creatinine, water, urea and electrolyte excretion was assessed from timed urine collections. Excretion of water, urea and electrolyte was normal during obstruction but increased dramatically immediately following relief (e.g. sodium 110 to 234 mmol/24 h). Values returned to normal by 2 weeks (sodium excretion 148 mmol/24 h). No further significant changes occurred up to 3 months. Mean 99mTc-DTPA and iohexol clearances during obstruction were 59.0 and 50.5 ml/min respectively. Following relief of obstruction, no significant improvement occurred at 2 weeks but did at 3 months (mean = 68.4 and 55.7 ml/min). Mean creatinine clearance during obstruction was 32.5 ml/min. This improved 2 days following relief to 46 ml/min. No further improvement was seen until 3 months (mean = 57.3 ml/min). It was concluded that recovery of renal function from obstructive injury occurs in two phases, an early tubular phase lasting up to 2 weeks and a later, predominantly glomerular phase, between 2 weeks and 3 months. There is some disparity between creatinine clearance and more accurate measurements of GFR which may be explained by tubular excretion of creatinine in the early phase of recovery.     

A unilateral section of the corticospinal tract at cervical level in primate does not lead to measurable cell loss in motor cortex

The effects of a unilateral interruption of the dorsolateral funiculus at cervical level on the survival of neurons in the motor cortex were investigated in macaque monkeys. The lesion was made on the left side at the transition region between the 7(th) and 8(th) cervical segments, above the motoneurons controlling hand muscles. As a result, the homolateral hand became paretic, although an incomplete recovery of manual dexterity took place during 2 months post-lesion. A quantitative anatomical assessment of pyramidal neurons in layer V was performed in the hindlimb area of the primary motor cortex and in the supplementary motor area (SMA proper). The pyramidal neurons were visualized using the marker SMI-32 and thus included the subpopulation of corticospinal neurons. These quantitative data demonstrated that the vast majority of the axotomized corticospinal (CS) neurons did not degenerate. Rather, their somata shrank, compared to the opposite hemisphere or to intact monkeys. This conclusion is in contrast to some previous studies in monkeys that argued for a substantial degeneration of motor cortex neurons as a result of transection of the corticospinal tract; yet in agreement with others that concluded the survival of most CS neurons. The survival of the majority of CS axotomized neurons is also consistent with the observation of numerous CS axons 1 mm above the cervical hemisection.