The role of the carotid body in mediating the cerebrovascular response to altered arterial carbon dioxide tension.

The role of the carotid bifurcation chemoreceptors in mediating the cerebrovascular response to altered arterial PCO2 has been suggested to be large. In the present study the cerebrovascular response to raised PCO2 was measured in a group of baboons before and after bilateral inactivation of the carotid bodies. The results suggest that these chemoreceptors do play a part in the cerebral vasodilator response to raised PCO2. The role of the carotid body, however, appears to be relatively minor as it only accounted for +/- 40% of the total response and became significant only at arterial PCO2 levels of more than 50 mm Hg. It is postulated that the peripheral chemoreceptors in the carotid bifurcation mediate part of the cerebrovascular response to altered PaCO2 but the role is quantitatively small.     

Effect of nitric oxide blockade by NG-nitro-L-arginine on cerebral blood flow response to changes in carbon dioxide tension.

The importance of nitric oxide (NO) for CBF variations associated with arterial carbon dioxide changes was investigated in halothane-anesthetized rats by using an inhibitor of nitric oxide synthase, NG-nitro-L-arginine (NOLAG). CBF was measured by intracarotid injection of 133Xe. In normocapnia, intracarotid infusion of 1.5, or 7.5, or 30 mg/kg NOLAG induced a dose-dependent increase of arterial blood pressure and a decrease of normocapnic CBF from 85 +/- 10 to 78 +/- 6, 64 +/- 5, and 52 +/- 5 ml 100 g-1 min-1, respectively. This effect lasted for at least 2 h. Raising PaCO2 from a control level of 40 to 68 mm Hg increased CBF to 230 +/- 27 ml 100 g-1 min-1, corresponding to a percentage CBF response (CO2 reactivity) of 3.7 +/- 0.6%/mm Hg PaCO2 in saline-treated rats. NOLAG attenuated this reactivity by 32, 49, and 51% at the three-dose levels. Hypercapnia combined with angiotensin to raise blood pressure to the same level as the highest dose of NOLAG did not affect the CBF response to hypercapnia. L-Arginine significantly prevented the effect of NOLAG on normocapnic CBF as well as blood pressure and also abolished its inhibitory effect on hypercapnic CBF. D-Arginine had no such effect. Decreasing PaCO2 to 20 mm Hg reduced control CBF to 46 +/- 3 ml 100 g-1 min-1 with no further reduction after NOLAG. Furthermore, NOLAG did not change the percentage CBF response to an extracellular acidosis induced by acetazolamide (50 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)     

Long term treatment and disease severity change brain responses to levodopa in Parkinson's disease

OBJECTIVES: Degeneration of nigrostriatal neurons and subsequent striatal dopamine deficiency produce many of the symptoms of Parkinson disease (PD). Initially restoration of striatal dopamine with oral levodopa provides substantial benefit, but with long term treatment and disease progression, levodopa can elicit additional clinical symptoms, reflecting altered effects of levodopa in the brain. The authors examined whether long term treatment affects the brain's response to levodopa in the absence of these altered clinical responses to levodopa. METHODS: Positron emission tomography (PET) measurements were used of brain-blood flow before and after an acute dose of levodopa in three groups: PD patients treated long term with levodopa without levodopa induced dyskinesias, levodopa naive PD patients, and controls. RESULTS: It was found that the PD group treated long term responded to acute levodopa differently from controls in left sensorimotor and left ventrolateral prefrontal cortex. In both regions, the treated PD group had decreased blood flow whereas the control group had increased blood flow in response to levodopa. Levodopa naive PD patients had little or no response to levodopa in these regions. Within the treated PD group, severity of parkinsonism correlated with the degree of abnormality of the sensorimotor cortex response, but not with the prefrontal response. CONCLUSIONS: It is concluded that long term levodopa treatment and disease severity affect the physiology of dopaminergic pathways, producing altered responses to levodopa in brain regions associated with motor function.     

Long term response to steroid therapy in Rasmussen encephalitis.

Rasmussen encephalitis (RE) is a severe and progressive focal epilepsy of unknown origin that leads to deterioration of motor and cognitive function. In a previous study, we described positive effect of high doses of steroids during the first year after the onset of RE. The objective of this study was to evaluate this therapy at long term. We reviewed 11 patients (7 girls and 4 boys) with RE of the right hemisphere (7) and the left (4) at a follow-up of 9+/-2 years. Age at onset of RE ranged from 2 to 14 years. Six patients had no benefit from steroid therapy and underwent hemispherotomy. Five had significant reduction of seizure frequency with disappearance of epilepsia partialis continua, and improved motor function. Of these, two died of unexpected sudden death 5 and 7 years after seizure control. Two others with initial response experienced progressive recurrence of seizures 1 to 4 years after the end of steroid therapy and required hemispherotomy. Finally, only one patient exhibited total cessation of seizures with steroids for 3 years, but seizures progressively recurred although the frequency was moderate. Our data confirm that although steroid treatment can be useful when given early in the course of RE, long term relapse can occur among the good responders requiring delayed hemispheric disconnection.     

Interstitial irradiation therapy of supratentorial gliomas by stereotaxic technique. Long term results

We report the long term results of interstitial irradiation therapy in patients suffering from malignant supratentorial gliomas. The radioisotopes implanted by stereotaxic technique were Au¹⁹⁸ grains in solid tumors and Y⁹⁰ colloidal solution in a cystic tumor. The therapy was always well tolerated. Minimum survival time after implantation was 9 months, maximum exceeded 52 months. In all cases interstitial irradiation therapy solved or drastically diminished the severe secondary epilepsy from which all the patients suffered.

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Sommario Gli autori riportano i risultati a lungo termine ottenuti nel trattamento di gliomi maligni sopratentoriali mediante irradiazione interstiziale con tecnica stereotassica. è stata utilizzato Au¹⁹⁸ in grani per i tumori solidi e Y⁹⁰ in un caso di astrocitoma cistico. Il trattamento è stato ben tollerato da tutti i pazienti. I tempi di sopravvivenza dopo irradiazione hanno variato da un minimo di 9 ad un massimo di 52 mesi. I pazienti presentavano tutti una severa sindrome comiziale che si risolse dopo il trattamento.

     

Modulation by muscarinic antagonists of the response to carbon dioxide challenge in panic disorder

BACKGROUND: Panic attacks can be induced in persons with panic disorder by inhalation of carbon dioxide. Hypercapnia also elicits a reflex hyperventilation, which is controlled in part by cholinergic mechanisms. This study investigated whether the exaggerated response to carbon dioxide in panic disorder (PD) can be modulated by antagonists of muscarinic cholinergic receptors. METHODS: Twelve patients with PD received biperiden hydrochloride (a muscarinic antagonist that crosses the blood-brain barrier), pirenzepine hydrochloride (a muscarinic antagonist that does not cross the blood-brain barrier), or placebo 2 hours before a 35% carbon dioxide-65% oxygen respiratory challenge (vs air as a placebo) on 3 separate days, in a double-blind, random crossover design. RESULTS: According to patients' self-ratings of subjective anxiety, inhalation of the carbon dioxide/oxygen mixture provoked a significant and intense response after treatment with pirenzepine and placebo. After biperiden treatment, however, hypercapnia elicited a response profile similar to that elicited by air, whereby subjective anxiety remained similar to preinhalation levels. CONCLUSIONS: Consistent with the hypothesis of the study, a centrally active muscarinic antagonist can block the response to carbon dioxide commonly observed in subjects with PD.     

替尼泊甙治疗恶性脑胶质瘤的远期结果

报道替尼泊甙－ＣＣＮＵ治疗恶性脑胶质瘤９６例随诊１～１０年的远期结果．男性６６例、女性３０例．年龄５～７４岁，平均３９．７岁。治疗周期总数４４８个，平均５个／例．远期结果计：ＣＲ１８例、ＰＲ２１例，ＲＲ率４０．７％；ＳＤ１９例、ＰＤ３７例、ＥＤ１例．存活率为：１年８５％、３年２６％、５年１４．６％、１０年１％。目前仍存活之１４例中已逾５年者５例．平均有效时限为ＣＲ组２１２周、ＰＲ组１２１周、ＳＤ组４６周、ＰＤ组１２周。平均存活时限为ＣＲ组２４１周、ＰＲ组１３３周、ＳＤ组５７周、ＰＤ组１８周。     

Acute carbon dioxide exposure in healthy adults: evaluation of a novel means of investigating the stress response

Acute hypercapnia was studied to assess its potential as a noninvasive and simple test for evoking neuroendocrine, cardiovascular and psychological responses to stress in man. A single breath of four concentrations of carbon dioxide (CO(2)), 5%, 25%, 35% and 50%, was administered to nine healthy volunteers in a randomized, single-blind fashion. Although no adverse effects occurred, most subjects were unable to take a full inspired vital capacity breath of 50% CO(2). In response to the remaining exposures, subjective and somatic symptoms of anxiety increased in a dose-dependent manner. Unlike 5% and 25% CO(2), 35% CO(2) stimulated significant adrenocorticotropic hormone and noradrenaline release at 2 min and cortisol and prolactin release at 15 min following inhalation. This same dose also provoked a significant bradycardia that was followed by an acute pressor response. No significant habituation of psychological, hypothalamic-pituitary-adrenal (HPA) or cardiovascular responses following 35% CO(2) was seen when this dose was repeated after 1 week. A single breath of 35% CO(2) safely and reliably produced sympathetic and HPA axis activation and should prove a useful addition to currently available laboratory tests of the human stress response.     

Long term exposure to heat protects against brain damage induced by closed head injury in the rat

Closed head injury leads to delayed tissue-edema, necrosis and impaired neurological function. In the present study the effect of chronic exposure to heat on the outcome of head injury in rats was investigated. Rats were held at ambient temperature of 24°C (CON) or 34°C (heat acclimated, ACC) for one month, before induction of trauma. Injury was induced by a weight drop device, falling over the left cerebral hemisphere. Twenty-four or 48 h later the rats were sacrificed and their brains removed for evaluation of edema (specific gravity or water content). Blood-brain barrier integrity (Evans blue extravasation) was evaluated 4 h after injury. One, 24 and 48 h after injury the rats were evaluated by a set of criteria which yields their clinical status (Neurological Severity Score - NSS). Forty-eight hours after trauma specific gravity of the contused hemispheres was 1.0389 ± 0.0019 and 1.0364 ± 0.0007 (P < 0.01) and water content 81.44 ± 1.28 and 84.17 ± 1.03% (P < 0.001), for ACC and CON rats, respectively. Lower degree of edema was also evident at 24 h suggesting slower rate of edema formation in ACC rats. Evans blue uptake by the contused hemisphere was 315 ± 61 and 50 ± 23 ng/g tissue in the CON and ACC rats, respectively (P < 0.001). Clinical recovery of the ACC rats was significantly better (P < 0.001) than that of the matched controls as exhibited at 48 h by median NSS values of: 10.8 (range 6-16) and 5 (range 4-6) for CON and ACC, respectively. Based on the present results we suggest that heat acclimation offers protection to rats subjected to head trauma.     

Comparative study of the FAIR technique of perfusion quantification with the hydrogen clearance method.

Arterial spin labeling magnetic resonance methods, including flow-sensitive alternating inversion recovery (FAIR), are becoming increasingly common for the noninvasive quantification of cerebral blood flow (CBF). This report compares the FAIR method with hydrogen clearance. The latter is an established, invasive technique for CBF measurement in animals. Paired readings of CBF were obtained in gerbils to maximize the degree of spatial and temporal correspondence between methods. Flow-sensitive alternating inversion recovery (50 averages, 6.7-minute measurement time) and hydrogen clearance measurements were made concurrently. Cerebral blood flow values measured by both techniques displayed an initial decrease because of the injurious effects of electrode insertion and subsequent recovery. Mixed model regression analysis, structural equations modeling, and a simple concordance correlation coefficient analysis were performed. No evidence of a marked systematic bias in the FAIR measurements was found; mixed model regression analysis yielded relative bias estimates of 0.4 (confidence interval: 3.0, 3.9) mL. 100 g-1. min-1 and -3.7 (-12.1, 4.7) mL. 100 g-1. min-1 at 20 and 100 mL. 100 g-1. min-1, respectively. The principal limitation of the FAIR technique was the magnitude of the random measurement error (imprecision), which had a standard deviation on the order of 10 mL. 100 g-1. min-1.     

A genetic study of the acute anxious response to carbon dioxide stimulation in man

People with panic disorder-agoraphobia and their relatives often react anxiously to CO(2)-enriched gas mixtures. Available data are not suited to disentangle genetic from common environmental causes of familial aggregation of CO(2) reactivity, nor provide quantitative estimations of the sources of trait variation. Three-hundred-forty-six twin pairs belonging to the general population-based Norwegian NIPH Mental Health Study underwent self-assessments of anxiety and of DSM-IV panic symptoms after inhalation of a 35%CO(2)-65%O(2) mixture. Two thresholds were employed - at sample's 75th and 90th percentiles of responses - to define provoked panic attacks and to calculate polychoric correlations. Variance components were estimated by structural equation modelling (SEM). For definitions of responses based on the sum of all 13 panic symptoms, SEM could not discriminate between shared environmental versus genetic causes of familial resemblance for provoked attacks. For definitions of responses based on global anxiety, or on the sums of those symptoms (dyspnea, dizziness, palpitations) with highest variance post-CO(2), the best-fitting models indicated additive genetic factors as the sole causes for within-family resemblance. Best-fit heritability estimates ranged from 0.42 to 0.57. Genetic and idiosyncratic environmental factors explain most of individual differences in reactivity to hypercapnia. Within-family similarities for this trait are largely explained by genetic determinants.     

Cerebrospinal fluid pressure alterations in experimental communicating hydrocephalus. Response of cerebrospinal fluid pressure to increase in arterial carbon dioxide tension

The response of cerebrospinal fluid (CFS) pressure to increased arterial carbon dioxide tension (PCO2) was evaluated in 5 control animals and 7 animals with experimentally induced communicating hydrocephalus. The CSF pressure in control dogs increased moderately in response to PCO2; in dogs with hydrocephalus, an increase in PCO2 produced a pronounced increase in CSF pressure accompanied by a simultaneous decrease in cerebral perfusion pressure. Progression of hydrocephalus can be explained by increased intracranial pressure, periventricular edema and cerebral ischemia.     

Cutaneous nerve activity in response to temperature changes of the cat's skin

Cutaneous nerve activity was recorded in response to changes in skin temperature. The presence of activity from the number of receptors which theoretically should be present in the area of skin innervated by the cutaneous nerve could be detected by the method of cross-correlation even if from small myelinated or unmyelinated fibers. No specific response in the small myelinated or unmyelinated afferents was detected in response to skin temperature changes in the range of 15–45 C. Activity recorded from the A, alpha-beta and A, delta-gamma groups in response to mechanical stimulation was not altered by skin temperature ranging from 15 to 45 C. With the temperature below this, the activity in both groups was markedly depressed. Above 45 C, there was some suppression of the A, alpha-beta, but more of the A, delta-gamma groups activity. Above 50 C, irreversible damage to the tissue occurred. Unmyelinated fiber activity in response to mechanical stimuli was increased above and below skin temperature deviating from room temperature. Below 7 C, the response was suppressed. Above 50 C, there is a large amount of C-fiber activity which occurs during the rapid change in skin temperature and this adapts out and C-fiber activity in response to mechanical stimuli is suppressed. The data derived from this study would support the spatial-temporal pattern of cutaneous sensibility as expounded by the “Oxford” group.     

Effects of carbon dioxide on hindlimb vascular resistance in the acute spinal cat

A cervical (C2) spinal section was carried out in anaesthetized, neuromuscularly blocked cats and the vascularly isolated hindlimbs were independently perfused at constant flow with blood taken from the abdominal aorta. One leg was denervated by sectioning the lumbar sympathetic chain. The animals were hyperventilated in 100% O2 and 5% or 10% CO2 in O2 was administered without altering the rate or tidal volume of the respirator. Increasing paCO2 (mm Hg) from 16.36 +/- 0.84 to 37.48 +/- 1.03 and to 62.23 +/- 2.23, induced a significant early vasoconstriction (P1) followed by a later more prolonged vasoconstriction (P2) in the innervated leg, while only a significant P2 response was present in the sympathetically denervated leg. A significant increase in systemic arterial pressure (SAP) was also observed with no change in heart rate (HR). After bilateral adrenalectomy increasing paCO2 from 17.16 +/- 0.66 to 37.96 +/- 1.21 and to 64.20 +/- 1.55, induced smaller but significant P1 and P2 responses in the innervated leg but only a significant P2 response was induced in the denervated leg. These results suggest that the early vasoconstriction was mainly due to activation of lumbar sympathetic neurons, while the late vasoconstriction was caused by the release of adrenal catecholamines and possibly other unidentified vasoconstrictor substances.