Exploring the pathogenesis of subarachnoid haemorrhages (SAH) using an animal model

Abstract

When an accident or other damage causes a bleed in the brain, the prognosis is bleak. The mortality rate is 45 per cent within the first month of the bleed occurring and 60 per cent of survivors do not return to a normal life. Naturally, SAH induces increased intracranial pressure and reduction of cerebral blood flow. The phenomena stimulate cytotoxic changes including apoptosis, inflammatory response, and oxidative stress. Even in cases where the bleed is caught in time, the damage done to the brain by those cytotoxic changes can have many dangerous consequences. Although it is known that the main determinant factors of SAH prognosis are early brain injury and cerebral vasospasm, the detailed mechanism are still undetermined. In addition, the SAH-induced brain damage could cause problems with cognitive functions; however, it can also have an affect elsewhere in the body. Professor Yu Hasegawa, of the Department of Pharmacology and molecular therapeutics, Kumamoto University Graduate School of Medical Science, Japan, is an expert in this field. He explains that a subarachnoid haemorrhage (SAH) occurs most often due to a cerebral aneurysm. "A cerebral vasospasm associated with SAH can happen from 4 to 14 days after the initial bleed and involves the tight constriction of the arteries running through the subarachnoid space," says Hasegawa. "This constriction leads to a lack of blood and subarachnoid bleeding itself induces microcirculatory disturbance. Then, both of them manifest as a delayed ischemic neurologic deficit and cerebral infarction." The cause of a cerebral vasospasm is not well understood and there is little effective treatment, however it is intimately linked with the effect the SAH has on whole sympathetic nervous system. Hasegawa is investigating the cause of this condition and thereby developing a treatment for it. He has implicated the central sympathetic nerve activation including periventricular nucleus of hypothalamus as the cause of the spasm and renal afferent sensory nerves as the control of the vasoconstriction. "The results of our study show that the suppression of central sympathetic nerve activity using renal denervation reduces vasospasm after SAH by maintaining sympathetic homeostasis," he outlines.