Early partial reperfusion in a new rat model of focal cerebral ischaemia

The influence of early partial reperfusion in a new rat model of focal cerebral ischaemia was investigated. Two groups, each of 30 adult male rats, were subjected to permanent occlusion of the right middle cerebral artery. The former, (group A) had an additional permanent occlusion of both common carotid arteries; the latter (group B) had a temporary carotid occlusion lasting for two hours. Mortality rate, evaluated within three days, was 70% ingroup A and 20% in group B. The mean size of cerebral infarcts was 63% in group A whereas it was 21% in group B. These data suggest that, in this animal model, early partial reperfusion is effective in reducing the mortality rate, and the size of the cerebral infarcts. Furthermore, this experimental model appears suitable for studies elucidating the role of reperfusion andlor other efforts in focal cerebral ischaemia.     

Prevention of symptomatic vasospasm after SAH by constant venous infusion of nimodipine

Sixty-one patients with SAH due to rupture of a cerebral aneurysm, classified in Grades I to IV according to Hunt and Hess, received a constant venous infusion of Nimodipine in a dose of 2mg/h for at least 14 days, followed by an oral administration of 60 mg/6 h for at least 4 days. Patients admitted after the 6th day of SAH, patients with SAH but without aneurysm on the angiogram and patients in Grade V were excluded. Mortality in 30 patients of Grades I-II was 3.3%, in 31 patients of Grades III-IV 42%. In the latter group 1 patient died due to cerebral vasospasm. Transient vasospasm occurred in 2 patients of Grades I-II. Recovery was complete in both cases. Thus, incidence of cerebral vasospasm was 4.9%, the incidence of poor-outcome-vasospasm even only 1.6%. The syndrome of cerebral vasospasm seems to be more than only constriction of cerebral vessels. The deleterious effects of Ca²⁺ shift into vascular cells and into neural cells which causes irreversible damage are discussed. Early administration of a specific 'cerebral' calcium antagonist like Nimodipine after SAH will prevent the intracellular Ca²⁺ overloading, thus protecting the neural cells and preventing Ca²⁺-induced smooth-muscle contraction of cerebral vessels, which encourages ischaemic deficits after SAH. The preventive use of Nimodipine has markedly reduced the incidence of symptomatic vasospasm in our clinic.     

Megadolichobasilar artery and acute cerebrovascular pathology

Sixteen patients with a megadolichobasilar artery and acute cerebrovascular symptoms are reported. All were explored by computerized tomography and vertebral angiography. Nine had transient ischaemic attacks or definitive ischaemic lesions, whereas 7 had subarachnoid or intracerebral haemorrhage. Among the patients with ischaemic troubles, vertebro-basilar insufficiency and pontine infarction were the most common clinico-radiological findings. Among the patients with intracranial haemorrhage, 4 had associated aneurysms or arteriovenous malformations, while 3 had subarachnoid or intracerebral haemorrhage with no vascular malformations on the angiograms. The possible relationships between the megadolichobasilar anomaly and the cerebral ischaemic or haemorrhagic pathologies are discussed also from a review of the pertinent literature.     

Effect of flunarizine on cerebral blood flow in baboons with or without focal cerebral ischaemia

In baboons with or without regional cerebral ischaemia (achieved by transorbital clip of the middle cerebral artery), cerebral blood flow (CBF) was measured using the intra-arterial Xenon-133 technique during steady-state, slight hypotension, and hypocapnia before and after administration of various doses of the calcium antagonist flunarizine (0.5 mg kg^–1, 1.0 mg kg^–1, or 10 μg kg^–1 min^–1 over 30 min). In normal baboons flunarizine did not alter CBF significantly, but at reduced blood pressure it increased CBF by 19.9% owing to exaggerated vasodilatory autoregulation. During hypocapnia flunarizine impaired the physiological reduction in CBF owing to reduced vasoconstriction. In baboons with cerebral ischaemia, CBF measurements were stable and comparable with those in a control group using an arterial clip unless flunarizine was added. In a group of five flunarizine-treated animals, mean CBF after positioning of the clip was higher than in the control group. However, the increase in mean CBF varied significantly between animals, indicating that a secondary reduction in CBF due to postischaemic pathophysiological processes was not prevented consistently.     

Changes in brain amino acid content induced by hyposmolar stress and energy deprivation

The changes in endogenous amino acids in brain extracellular and intracellular compartments evoked by hyposmotic stress and energy deprivation were compared. Tissue content and release of ten amino acids were measured simultaneously in rat hippocampal slices by means of high performance liquid chromatography Hyposmotic stress induced a large release of taurine (25568 pmol mg-7 protein), and a smaller release of glutamate, accompanied by an inverse change in tissue content. Adding mannitol to correct osmolarity blocked these changes. Energy deprivation caused an increase in the release of all amino acids except glutamine. The release was particularly large for glutamate and GABA (31141 and 13282 pmol mg^–1 respectively). The intracellular concentrations were generally reduced, but the total amount of the released amino acids increased. In contrast to the effect seen during hyposmolar stress, mannitol enhanced the changes due to energy deprivation. The results show that hyposmolar stress and energy deprivation cause different content and release profiles, suggesting that the mechanisms involved in the two situations are either different, or modulated in different ways. The intracellular amino acid depletion seen during energy deprivation shows that increased outward transport is probably a primary eventL, and increased amino acid formation likely secondary to this release. [Neurol Res 1995; 17: 402–408]     

Effect of stimulation of the dorsal aspect of the cervical spinal cord on ’Iocal cerebral blood flow and EEG in the cat

Abstract

Currently there is considerable interest in electrical stimulation of the dorsal aspect of the cervical spinal cord as a potentially effective therapy for persistent vegetative patients. The authors assessed change in the local cerebral blood flow (LCBF) and electroencephalogram (EEe) in the cat following spinal cord stimulation (SCS). In 31 adult cats under isoflurane anesthesia, an electrode for SCS was introduced epidurally to the midline of the C2-C3 segment. Stimulation was performed at 25 Hz and 0.7 msec for30 min. These animals were divided into five groups by the voltage: (1) 2V (n = 7), (2) 4V (n = 7), (3) 6V (n = 7), (4) 4V with intravenous injection of muscarinic cholinergic agents - atropine sulfate (n =5), and (5) sham-operated control (n = 5) without stimulation. LCBF was measured by laser Doppler flowmetry through bilateral small burr holes at the parietal area during and 60 min after stimulation. At 2~ LCBF increased only during SCSI then returned to the pre-stimulated level, while the increase continued until the end of the experiment at 4Vand 6V. The increase in LCBF was not affected by atropine sulfate. EEe showed spike and wave or polyspikes after SCS in two animals of the 6V group, but not in the 2V and 4V groups, and moreover a moderate increase ofthe background activity at only 4V. The present data suggested that SCS at 4Vcan provide the appropriate microcirculatory enhancement with less harmful influence which continues to increase 30 min after SCSI although the exact mechanism should be elucidated continuously. Within the limitation of animal experiments, this study could provide the logical basis for determining the condition of SCS. [Neural Res 2000; 22: 386-392]     

Endothelium-dependent relaxation and vasospasm in the single-hemorrhage canine model

Abstract

We have investigated the relationship between angiographic vasospasm and the ability of spastic vessels to relax in response to agents which promote release of endothelium derived relaxing factor. Vasospasm was induced in dogs by the 'single hemorrhage' technique. Animals received a single intracisternal injection of blood, blood activated with thromboplastin or collagen, or inert material, and angiograms were obtained day 0 and day 7. Vasospasm was estimated by measuring the ratio of the diameter of the vessel before and after treatment. Rings of cerebral artery obtained from these animals were suspended in a standard organ- bath arrangement, contracted with prostaglandin F2(X and then treated with increasing doses of adenosine triphosphate or bradykinin, both of which cause relaxation by an endothelium-dependent process. The arteries from animals with moderate to severe vasospasm showed a response to bradykinin and adenosine- triphosphate which was reduced, absent or converted to a contraction, when compared with normal vessels. Vessels in which vasospasm was mild or absent relaxed as expected to these agents. The reduction in vessel diameter showed a highly significant correlation with the reduction in relaxation to bradykinin or adenosine-triphosphate. These results have demonstrated that impairment of endothelium-dependent vasorelaxation correlates with the existence of vasospasm. [Neurol Res 1996; 18: 553-558]     

Anoxic depolarization determines ischemic brain injury

Abstract

To clarify the role of anoxic depolarization (AD) in ischemic brain injury, we examined the correlation between AD and ischemia-induced neuronal injury. Twenty-eight rats underwent transient forebrain ischemia with lowering of blood pressure and bilateral carotid occlusion while direct current shiftslelectrocorticogram, and cortical blood flow (COBF) were epidurally recorded from the right parietal cortex. One week later the right parietal cortex was studied histopathologically. AD appeared 0.5-3.0 min after carotid occlusion in 21 of28 animals. Circulation was reinitiated 75 min afterAD onset in 77 rats (group A) and 10 min after onset in 70 rats (group B). AD did not develop during 20 min of ischemia in 7 rats (group C). All 72 rats (6 from group A and 6 from group B) in which CoBF decreased below 9.5% of control flow exhibited AD. Histopathologic examination disclosed massive neuronal necrosis in 5 of the 6 group A animals with marked flow reduction but in none from group B. CoBF fell between 9.5% and 20% in 74 rats, among these, AD appeared in 9 (5 from group A and 4 from group B) but not in 5 (group C). Massive neuronal necrosis was demonstrated in 3 of5 rats from group A. Ischemic neuronal changes were absent or minimal in only 7/5 ofgroup A animals, a much lower fraction than in group B (4/4, p<0.05) or in group.C (5/5/, p<0.05). When CoBF remained above 20% of control flow during ischemia (2 rats) no AD or irreversible injury occurred. The present study suggests that AD is a more reliable determinant of irreversible brain injury than degree of CBF reduction, and also demonstrates that 75 min is the critical duration of AD for irreversible brain injury at brain temperatures around 37° C. [Neural Res 1998; 20: 343-348]