Effect of stimulation of the medullary reticular formation on brain water content in cold injured brain

Recently it has been reported that stimulation of the medullary reticular formation (MORF) directly decreased the cerebral vasomotor tonus by intrinsic pathways of the central nervous system and resulted in increases in the cerebral blood volume (CBV) and intracranial pressure (ICP). Decreased cerebral vasomotor tonus has been postulated to enhance water movement from vascular cavity to the brain tissue. So this study was carried out to investigate the effect of stimulation of MORF on brain water content in cold injured brain, which has been confirmed to have a similar pathophysiological nature to cerebral contusion. Experiments were conducted on 28 cats. The cold injury was inflicted by applying a freezing prove of -50 degrees C for 1 minute directly on the dura. 17 hours after cold injury, animals were divided into 4 groups, i.e. Group I: cold lesion only, Group II: electrical stimulation of MORF (1 msec, 10 V, 50 Hz) for 10 minutes, which was repeated 4 times with 5 minutes interval, Group III: the same stimulation of MORF for 40 minutes as Group II, with spinal cord transection at C-2 level before the stimulation to eliminate vasopressor response, Group IV: administration of Angiotensin II for 60 minutes to elevate blood pressure at the same level as observed during the stimulation. In each group, 18 hours after making lesion, the brain was removed and water content was determined by specific gravimetric technique and expressed as percent g water/g tissue.(ABSTRACT TRUNCATED AT 250 WORDS)     

Vasopressin in the cerebrospinal fluid of febrile children with or without seizures

Immaturity in water and electrolyte balance in the brain has been considered to increase the susceptibility of young animals and children to febrile convulsions (FCs). Arginine-vasopressin (AVP) is involved in the regulation of several centrally mediated events such as modulation of fever and the ease with which water permeates into and out of the brain. To evaluate the possible role of AVP in the control of water balance and susceptibility to convulsions during fever we measured the AVP concentration in the cerebrospinal fluid (CSF) and plasma of febrile children with or without convulsions. The febrile population consisted of 47 children, of whom 29 experienced seizures during fever. Seven children with epileptic symptoms and 18 children without seizures were included as nonfebrile controls. The CSF AVP concentration in febrile children without seizures and in nonfebrile convulsive children was significantly lower (0.60 ± 0.07 pmol / 1, mean ± SEM,P < 0.01 and 0.65 ± 0.19 pmol/l,P < 0.05, respectively) than in nonfebrile children without convulsions (0.83 ± 0.06 pmol/1). However, the levels of CSF AVP were not significantly different in children with FCs (0.71 ± 0.06 pmol/1) compared with other groups. CSF AVP correlated with the CSF osmolality (r = 0.33, P = 0.02). No statistical differences in plasma AVP levels between the groups could be found. The present data provide support for the hypothesis of synchronous regulation of osmolality and AVP concentration in CSF. During fever the concentration of CSF AVP was lower in nonconvulsive children compared with nonfebrile nonconvulsive children. CSF AVP levels were not affected in febrile children by convulsions.     

Effects of dehydration and salt-loading on hypothalamic vasopressin mRNA level in male and female rats

Experiments were carried out on 9- to 11-week-old male and female Sprague-Dawley rats. Dot-blot analysis and 3′-end digoxigenin-labeled 26mer oligonucleotide probe were used in the investigation of vasopressin (AVP) mRNA level in the hypothalamus of male and female rats. The normal hypothalamic AVP-mRNA level in males was 48% higher than that in females (P < 0.05). Plasma osmolality was also higher in males than in females (P < 0.05). In dehydrated rats, the hypothalamic AVP-mRNA level was 2.47 and 1.98 times in females (P < 0.001) and males (P < 0.01), respectively, as much as in their normal controls; the difference in hypothalamic AVP-mRNA level between dehydrated females and males was statistically insignificant. Plasma osmolality was higher in dehydrated females than in dehydrated males (P < 0.01). In salt-loaded rats, hypothalamic AVP-mRNA level was 2.47 and 2.17 times in females (P < 0.001) and males (P < 0.01), respectively, as much as in their controls. The difference in hypothalamic AVP-mRNA level between salt-loaded males and females was not statistically significant. Plasma osmolality in salt-loaded females was also higher than that in salt-loaded males (P < 0.001). These findings indicate that there is sex difference in hypothalamic AVP mRNA level and plasma osmolality under normal conditions; during dehydration and salt-loading AVP mRNA level increases and the difference in AVP mRNA level between males and females becomes insignificant.     

Brain injury from marked hypoxia in cats: role of hypotension and hyperglycemia

The present study identifies several factors that govern brain pathologic response to marked hypoxia. None of 13 cats exposed to 25 minutes of marked hypoxia (FiO2 = 3.4%; PaO2 = 17 +/- 3 mm Hg, S.D.) that maintained mean arterial blood pressure (MABP) greater than 65 mm Hg were brain injured after reoxygenation and long term survival. In contrast, 12 of 13 exposed to the same hypoxia but that experienced reductions in MABP less than 45 mm Hg for 4 +/- 1 minutes developed a pattern of brain injury closely resembling that of humans surviving in a persistent vegetative state after cardiorespiratory arrest. Higher serum glucose and lactate concentrations and lower blood pH values significantly correlated with development of hypotension during hypoxia. Four of 8 cats exposed to 21 minutes of marked hypoxia followed by 4 minutes of 100% N2 breathing that also led to hypotension similarly developed brain injury. Among the hypoxic/hypotensive cats the magnitude of the hyperglycemic response to hypoxia as modulated by 0, 1, or 2 days of preexposure fasting, strongly correlated with occurrence and extent of brain damage. Peak cisterna magna CSF lactate concentrations 10 to 30 minutes into recovery distinguished those animals that remained brain-intact (less than 13 mM) from those that developed brain damage (greater than 15 mM) with 100% accuracy. Seven cats developed delayed cardiogenic shock 3 to 12 hours into the recovery period. This outcome was predicted by blood pH values less than 6.70 shortly after resuscitation while all 27 surviving cats exhibited values greater than 6.80.     

Antiepileptic Properties of Cerebrospinal Fluid After Activation of the Antiepileptic System of the Brain

Intraventricular injection of cerebrospinal fluid (CSF) obtained from cats with chronic electrical stimulation of cerebellar vermal cortex resulted in suppression of epileptic foci activity in cat brain cortex, an increase in time to first seizure, and weakening of generalized seizures in rats. The CSF obtained from cats after electroshock seizures induced less pronounced, although significant antiepileptic action in comparison with the CSF of cats with cerebellar stimulation on the model of generalized seizures in rats. The antiepileptic action of CSF obtained from cats with electrostimulation of cerebellar vermis and from electroshock cats is due to appearance of peptide factors in CSF.     

Cerebrospinal fluid neurohypophysial peptides in benign intracranial hypertension.

The cerebrospinal fluid (CSF) concentrations of arginine vasopressin (AVP) and oxytocin (OT) were investigated both in patients with benign intracranial hypertension and in age and sex matched controls. Twenty eight lumbar punctures were performed on 15 patients with benign intracranial hypertension as part of their routine investigation and therapy. All patients had raised intracranial pressure (27.4, SE 1.7 cm.CSF). CSF AVP levels were significantly elevated in benign intracranial hypertension (2.1, SE 0.3 pmol/l) compared with controls (0.7, SE 0.1 pmol/l, p less than 0.001) but CSF OT concentrations were similar in both groups. CSF osmolality and plasma AVP and osmolality were identical in patients and controls. There was no correlation between CSF AVP concentration and intracranial pressure. The selective elevation of AVP in CSF may be of importance in the pathogenesis of raised intracranial pressure in benign intracranial hypertension.     

Cerebrospinal fluid and plasma concentrations of oxytocin and vasopressin during parturition and vaginocervical stimulation in the sheep

Simultaneous blood and cerebrospinal fluid (CSF) samples were taken from conscious sheep before, during and after parturition. Concentrations of plasma and CSF oxytocin were significantly elevated during contractions and particularly at birth. Mean prepartum CSF concentrations of oxytocin were around 55% of those found in plasma but postpartum they were up to 2-fold higher than those in plasma. Plasma concentrations of oxytocin were only significantly elevated, compared to prepartum levels, for 15 min postpartum whereas those in CSF were increased for the whole of the 120 min postpartum sampling period. Plasma, but not CSF, concentrations of arginine-vasopressin (AVP) were significantly raised during contractions and birth, and for 15 min postpartum. During the prepartum period CSF AVP concentrations were 67% of those found in plasma whereas at birth plasma levels were 10-fold higher than in CSF. In a separate experiment it was shown that 5 min of mechanical vaginocervical stimulation also stimulated significant increases in CSF and plasma oxytocin concentrations and in plasma vasopressin. Results support previous work suggesting an important role for central oxytocin release in the postpartum induction of maternal behavior and demonstrate that elevated concentrations of oxytocin in the CSF are present for a greater period than in blood. Elevated plasma AVP concentrations during contractions, birth or vaginocervical stimulation may be stimulated by stress associated with these stimuli.     

Central orexin-A activates hypothalamic-pituitary-adrenal axis and stimulates hypothalamic corticotropin releasing factor and arginine vasopressin neurones in conscious rats

The effects of centrally injected orexin-A on plasma adrenocorticotropin (ACTH) and corticosterone levels and corticotropin releasing factor (CRF) and arginine vasopressin (AVP) mRNA in the parvocellular cells of the paraventricular nucleus (PVN) of the rat were investigated. In animals implanted previously with a lateral brain ventricle and femoral artery cannula, a single i.c.v. injection of orexin-A (10 microg/rat) resulted in a rapid, significant increase in plasma ACTH and corticosterone concentrations. Plasma ACTH reached a peak (12.5-fold greater than basal levels) at 30 min, which was maintained over 120 min before declining towards control levels by 240 min. Plasma corticosterone concentrations reached a peak (6.7-fold greater than basal levels) at 30 min. Orexin-A at a higher dose (30 microg/rat) also produced a rapid increase in plasma ACTH and corticosterone concentrations. The area under the curve for plasma levels of ACTH was similar for both doses of orexin-A. In a second study, orexin-A (10 microg/rat) was injected i.c.v. and brains and pituitaries were rapidly removed after 240 min. In situ hybridization histochemistry revealed that CRF and AVP mRNA levels were significantly increased in the parvocellular cells of the PVN. Pro-opiomelanocortin mRNA levels in the pituitary gland were not significantly elevated in response to orexin-A. These results suggest that orexin-A is able to act centrally to activate the hypothalamic-pituitary-adrenal axis involving stimulation of both CRF and AVP expression.     

Changes in intracranial pressure elicited by electrical stimulation of the brainstem reticular formation in spinal cats with vagotomy

The momentary changes in intracranial pressure (ICP) were explored using electrical stimulation of the brainstem reticular formation and the nucleus fastigii of the cerebellum in cats under artificial ventilation after spinalization (C2) and vagotomy. Regions that yielded an increase in ICP in the arterial pressor area were: the central part of the pontine recticular formation, the dorsal medullary reticular formation, the central part of the medullary reticular formation, and the nucleus fastigii of the cerebellum; and one region in the arterial depressor area was the paramedial and ventral medial region of the medullary reticular formation. Since the arterial blood pressure and respiration was maintained constant during electrical stimulation by spinalization and vagotomy, the increase in ICP in the cranium, a semi-closed box, momentarily reflected an increase in cerebral blood volume due to cerebral vasodilatation. It is suggested that excitation of cell bodies or fibres within these regions may produce cerebral vasodilatation.     

Effects of electrical stimulation on intracranial pressure and systemic arterial blood pressure in cats. Part I: Stimulation of brain stem

It has been suggested that brain stem activity is involved in the occurrence of pressure waves. Different sites in the brain stem were activated by electrical stimulation in cats anaesthetized with sodium pentobarbital, to produce an increase in intracranial pressure (ICP) similar to the pressure waves. Then the effect of artificial ventilation on the occurrence of the pressure wave-like response produced under spontaneous respiration was examined since Lundberg's A-waves appear even in artificial ventilation, and B-waves are effaced during artificial ventilation. This results in a brain stem map of ICP and systemic arterial blood pressure (BP) produced by electrical stimulation during spontaneous respiration. Stimulation of the rostral medullary reticular formation produced a rise in ICP and BP in association with a change in the rhythm of the spontaneous respiration; with artificial ventilation, stimulation produced a rise in BP but ICP kept almost at the same level. However, the rise in ICP that was produced by stimulation of the caudal medullary reticular formation during spontaneous respiration also occurred with a depressor response of BP during controlled ventilation. The pressure wave-like responses could be classified, therefore, into two types. One was the response seen during both spontaneous and controlled ventilation, which we designated the 'alpha' wave. The other was the response seen only during spontaneous ventilation, the 'beta' wave. These observations suggest that the origins of A- and B-waves may be related to those of 'alpha' and 'beta' waves, respectively.     

Effects of electrical stimulation on intracranial pressure and systemic arterial blood pressure in cats: Part I: Stimulation of brain stem

It has been suggested that brain stem activity is involved in the occurrence of pressure waves. Different sites in the brain stem were activated by electrical stimulation in cats anaesthetized with sodium pentobarbital, to produce an increase in intracranial pressure (ICP) similar to the pressure waves. Then the effect of artificial ventilation on the occurrence of the pressure wave-like response produced under spontaneous respiration was examined since Lundberg’s A-waves appear even in artificial ventilation, and B-waves are effaced during artificial ventilation. This results in a brain stem map of ICP and systemic arterial blood pressure (BP) produced by electrical stimulation during spontaneous respiration. Stimulation of the rostral medullary reticular formation produced a rise in ICP and BP in association with a change in the rhythm of the spontaneous respiration; with artificial ventilation, stimulation produced a rise in BP but ICP kept almost at the same level. However, the rise in ICP that was produced by stimulation of the caudal medullary reticular formation during spontaneous respiration also occurred with a depressor response of BP during controlled ventilation. The pressure wave-like responses could be classified, therefore, into two types. One was the response seen during both spontaneous and controlled ventilation, which we designated the ‘α’ wave. The other was the response seen only during spontaneous ventilation, the ‘β’ wave. These observations suggest that the origins of A- and B-waves may be related to those of ‘α’ and ‘β’ waves, respectively.     

Medullary mechanisms for eating and grooming behaviors in the cat

Electrical stimulation of localized regions of the medullary reticular formation induced well-coordinated eating and grooming behaviors in cats. The findings suggested that these behaviors resulted from the activation of specific sensorimotor mechanisms, rather than from the induction of generalized drive states. Eating and grooming, however, were directed and goal dependent, and not merely motor automatisms. Other elicited responses included escape behavior and fragmentary components of threat behavior. The findings contribute to the growing view that the lower brain stem may play an important role in the elaboration and control of complex species-characteristic behaviors.     

Central and peripheral release of vasopressin and oxytocin in the conscious rat after osmotic stimulation

Vasopressin (AVP) and oxytocin (OXT) were measured by radioimmunoassay in push-pull perfusates and tissue samples of various brain areas, plasma and cerebrospinal fluid (CSF) of male rats in response to osmotic stimulation. Hypertonic saline caused a significant rise in plasma AVP and OXT and different changes in peptide contents, in the septum and hippocampus at 30 and 60 min after intraperitoneal injection. Push-pull perfusion (20 microliters artificial CSF/min, 30-min periods) of the septum and dorsal hippocampus of conscious, unrestrained animals revealed a significant, stimulus-evoked release of both AVP and OXT. This release was: (1) not always reflected by corresponding changes in the regional peptide content; (2) simultaneous with the peripheral release from the posterior pituitary; and (3) probably the result of synaptic/parasynaptic events as suggested by use of agents in the artificial CSF which either inhibit or facilitate the release from intact fibre terminals.     

Evaluation of the secretory pattern of plasma arginine vasopressin in stroke patients

Arginine vasopressin (AVP) may play a role in the development of ischemic brain edema and/or cerebral vasospasm. Data available on AVP plasma levels in ischemic stroke are few and discordant. In order to ascertain whether changes in AVP plasma levels occur in ischemic stroke, plasma AVP levels, plasma osmolality and mean arterial pressure were determined in 24 patients with unprecedented ischemic cerebral infarction and in 15 controls over a 24-hour period. In stroke patients, mean 24-hour plasma AVP levels (7.2 +/- 0.8 ng/l) were higher (p < 0.05) than in control subjects (2.4 +/- 0.3 ng/l), and correlated with the severity score of the neurologic deficit and the mean size of the lesion. In patients with a more severe neurologic deficit, the mean 24-hour plasma AVP levels (8.7 +/- 1.0 ng/l) were higher than in patients with a less severe neurologic deficit (5.2 +/- 0.8 ng/l). Data indicate that in ischemic stroke an increased AVP secretion occurs independently of osmotic or baroreceptorial mechanisms. The possibility that AVP may play a role in neuronal cell damage following cerebral ischemia warrants further attention.     

Brain stem control of masseteric reflex activity during sleep and wakefulness: medulla.

The present study was undertaken to examine possible involvement of the anterior medulla in the phenomenon of reticular response-reversal. This phenomenon occurs when conditioning stimulation, delivered to the pontomesencephalic reticular core, produces an increase in masseteric reflex excitability during wakefulness and quiet sleep, but induces a suppression of excitability during active sleep. Thirteen cats were implanted with chronic electrodes which were used to deliver a test stimulus to the mesencephalic Vth nucleus to evoke the masseteric reflex, to apply conditioning stimuli to sites at the pontomedullary junction, and to monitor the electroencephalogram (EEG), electrooculogram (EOG), and electromyogram (EMG) in the freely moving cat during wakefulness, quiet sleep, and active sleep. During wakefulness and quiet sleep, conditioning stimulation reliably produced reflex facilitation (principally from medial sites) which lasted 10 to 40 ms with a peak effect at 20 ms. During active sleep, the same stimulation produced reflex suppression with a similar time course. Time course patterns obtained from sites at the pontomedullary junction resembled those generated from rostral brain stem regions with the exception that many medullary sites yielded short latency reflex suppression throughout wakefulness, quiet sleep, and active sleep. In addition, lower thresholds of conditioning current were found to induce reflex facilitation and suppression from sites at the medullary level than were required at the pontine or mesencephalic levels.     

Neurotoxic lesions of the dorsolateral pontomesencephalic tegmentum-cholinergic cell area in the cat. I. Effects upon the cholinergic innervation of the brain

Kainic acid was injected bilaterally (4.8 micrograms in 1.2 microliter each side) into the dorsolateral pontomesencephalic tegmentum of cats in order to destroy cholinergic cells which are located within the pedunculopontine tegmental (PPT), laterodorsal tegmental (LDT), parabrachial (PB), and locus ceruleus (LC) nuclei in this species. The neurotoxic lesions resulted in the destruction of the majority (approximately 60%) of choline acetyltransferase (ChAT)-immunoreactive neurons and a minority (approximately 35%) of tyrosine hydroxylase (TH)-immunoreactive neurons, as well as in the destruction of other chemically unidentified neurons, in the region. The effects of these lesions upon the cholinergic innervation of the brain were investigated by comparison of brains with and without lesions which were processed for acetylcholinesterase (AChE) silver, copper thiocholine histochemistry and ChAT radio-immunohistochemistry. In the forebrain, a major and significant decrease in AChE staining, measured by microdensitometry, and associated with a decrease in ChAT immunoreactivity was found in certain thalamic nuclei, including the dorsal lateral geniculate, lateral posterior, pulvinar, intralaminar, mediodorsal and reticular nuclei. All of these nuclei receive a rich cholinergic innervation evident in both AChE histochemistry and ChAT immunohistochemistry. No significant difference in AChE staining or ChAT immunoreactivity was detected in other thalamic nuclei or in the subthalamus, hypothalamus or basal forebrain. In the brainstem, a significant decrease of AChE staining and ChAT immunoreactivity was found in the superior colliculus and the medullary reticular formation, where ChAT-immunoreactive fibers were moderately dense in the normal animal. These results indicate that the pontomesencephalic cholinergic neurons may influence the forebrain by major projections to the thalamus, involving both relay and non-specific thalamocortical projection systems, and thus act as an integral component of the ascending reticular system. They may influence the brainstem by projections onto deep tectal neurons and other reticular neurons, notably those in the medullary reticular formation, and thus also affect bulbar and bulbospinal systems.     

Role of arginine vasopressin V1 and V2 receptors for brain damage after transient focal cerebral ischemia.

Brain edema formation is one of the most important mechanisms responsible for brain damage after ischemic stroke. Despite considerable efforts, no specific therapy is available yet. Arginine vasopressin (AVP) regulates cerebral water homeostasis and has been involved in brain edema formation. In the current study, we investigated the role of AVP V1 and V2 receptors on brain damage, brain edema formation, and functional outcome after transient focal cerebral ischemia, a condition comparable with that of stroke patients undergoing thrombolysis. C57/BL6 mice were subjected to 60-min middle cerebral artery occlusion (MCAO) followed by 23 h of reperfusion. Five minutes after MCAO, 100 or 500 ng of [deamino-Pen(1), O-Me-Tyr(2), Arg(8)]-vasopressin (AVP V1 receptor antagonist) or [adamantaneacetyl(1), O-Et-D-Tyr(2), Val(4), Abu(6), Arg(8,9)]-vasopressin (AVP V2 receptor antagonist) were injected into the left ventricle. Inhibition of AVP V1 receptors reduced infarct volume in a dose-dependent manner by 54% and 70% (to 29+/-13 and 19+/-10 mm3 versus 63+/-17 mm3 in controls; P<0.001), brain edema formation by 67% (to 80.4%+/-1.0% versus 82.7%+/-1.2% in controls; P<0.001), blood-brain barrier disruption by 75% (P<0.001), and functional deficits 24 h after ischemia, while V2 receptor inhibition had no effect. The current findings indicate that AVP V1 but not V2 receptors are involved in the pathophysiology of secondary brain damage after focal cerebral ischemia. Although further studies are needed to clarify the mechanisms of neuroprotection, AVP V1 receptors seem to be promising targets for the treatment of ischemic stroke.     

Central vasopressin pretreatment sensitizes phosphoinositol hydrolysis in the rat septum

Previous in vivo and in vitro studies have demonstrated that exposure of the brain to arginine vasopressin (AVP) can potentiate various responses to a second central challenge with AVP. To determine whether this sensitization is mediated by changes at the receptor level, we investigated the effects of AVP on the phosphoinositide metabolism in septal slices prepared from rats centrally pretreated with saline or AVP. Addition of vasopressin (10(-7) M, 10(-6) M) to septal slices from saline-pretreated rats failed to elicit a significant stimulation of inositol-1-phosphate (IP1). In contrast, AVP (10(-7) M) significantly stimulated IP1 release in septal slices prepared from rats pretreated intracerebroventricularly (i.c.v.) 24 h earlier with 10 or 100 ng AVP. Pretreatment with the same i.c.v. doses of AVP also induced a significant enhancement of the carbachol-induced stimulation of IP1 release, but i.e.v. pretreatment with carbachol did not stimulate the IP1 release in response to AVP. Our results suggest that a novel facilitation of phosphoinositide metabolism can be induced by central AVP pretreatment.     

Inhibition of spinal reflexes by paramedian reticular nucleus

The inhibitory actions of the paramedian reticular nucleus (PRN), and its neighbouring structures, i.e., midline raphe nuclei (MRN) and dorsal medullary depressor area (DMD) on the knee jerk (KnJ) and crossed extension movement (CEM) induced by central sciatic stimulation and on the L5 ventral root response (EVRR) evoked by central tibial stimulation, were studied in cats under urethane (400 mg/kg) and alpha-chloralose (40 mg/kg) anesthesia alone, IP or further paralyzed with atracurium besylate (0.5 mg/kg/30 min), IV. Electrical stimulation of the above areas with rectangular pulses (80 Hz, 1.0 msec, 100-200 microA) decreased systemic arterial blood pressure (SAP) in an average value of: 36 +/- 3 mmHg for PRN; 19 +/- 2 mmHg for MRN; and 23 +/- 3 mmHg for DMD. The KnJ and CEM were almost completely suppressed by simultaneous PRN stimulation. The EVRR, including mono- and polysynaptic spinal reflexes with transmission velocity from 10 to 60 m/sec or above, were also suppressed. MRN stimulation only inhibited the KnJ, CEM and polysynaptic spinal reflexes with transmission velocities between 25 and 60 m/sec, but facilitated spinal reflexes with conduction velocities below 10 m/sec. On the other hand, DMD stimulation resulted in small suppression of KnJ, CEM and inhibition of polysynaptic spinal reflexes with conduction velocities between 25 and 60 m/sec. Even though MRN and DMD partially inhibited polysynaptic spinal reflexes, the magnitude of such inhibition was much smaller than that produced by PRN (-20% and -22% vs. -48%). The above-mentioned PRN effects on SAP and EVRR persisted in chronic animals decerebellated 9-12 days before.(ABSTRACT TRUNCATED AT 250 WORDS)