beta-endorphin and Subarachnoid-Hemorrhage

The opiate antagonist naloxone was suggested for the amelioration of cerebral ischemia after subarachnoid hemorrhage (SAH) following the 1981 report of clinical improvement of ischemic deficits in 2 patients. The deficit in 1 patient was exacerbated by morphine, suggesting that analgesics acting on opiate receptors should be avoided after SAH, and this would include codeine phosphate and dihydrocodeine, both widely used for post-SAH headache. We studied 21 consecutive patients with aneurysmal SAH whose condition was worse than Grade 1 on the Hunt and Hess scale. A single observer graded them to avoid interobserver error, and they were also given a score on the Glasgow coma scale. Each patient was then given an intravenous injection of 0.9% saline as placebo or 0.4 mg (7 patients) or 2.0 mg (14 patients) of naloxone. Five minutes later, the same observer regraded the patient. After 30 minutes, a second injection of placebo or naloxone was given, and the patient was regraded a third time. Each patient received placebo in one injection and naloxone in the other, but the order was randomized and unknown to the observer. There was no beneficial effect of 0.4 mg of naloxone after aneurysmal SAH, and we did not find an elevated level of the endogenous opiate beta-endorphin in the cerebrospinal fluid in the majority (6 of 8 of the patients in whom it was assayed). Five of the patients given 2.0 mg of naloxone did improve transiently, and none deteriorated after the drug, suggesting that naloxone in a high dose may have a place in the management of some post-SAH deficits.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; beta-Endorphin; Brain Ischemia; Cerebrospinal Fluid; Endorphins; Female; Humans; Intracranial Aneurysm; Male; Middle Aged; Naloxone; Rupture, Spontaneous; Subarachnoid Hemorrhage

The chronic stage of vasospasm occurring several days after subarachnoid hemorrhage (SAH) is characterized by the development of histopathologic changes in cerebral arteries causing cerebral ischemia. Numerous experimental data indicate the involvement of immune mechanisms in the angiopathy caused by SAH. Endogenous opioids play also an important role in the ischemic lesions of the brain. Corticotropin releasing hormone (CRH) induces the release of beta-endorphin (beta-END) from hypothalamic neurons and also from mononuclear white blood cells. The function of CRH and beta-END in vasospasm following SAH and the interrelationship between neuroendocrine and immune changes requires further elucidation. In the present study we investigated the influence of CRH injected into cerebral cisterna magna (CM) of rats on beta-END-like level in cerebrospinal fluid (CSF) in acute and chronic phase of cerebral vasospasm following artificial SAH. Acutely CRH induced a significant rise of beta-END-like in CSF both in SAH and sham SAH rats. However, in rats subjected to SAH, a single injection of CRH caused a prolonged rise of 5-END in CSF, which was also seen 2 days after SAH, during the chronic phase of vasospasm. The obtained results indicate that CRH increases neuroendocrine changes induced by SAH, probably by an activation of immune cells involved in the patomechanism of chronic vasospasm.

Topics: Acute Disease; Animals; beta-Endorphin; Catheterization; Chronic Disease; Cisterna Magna; Corticotropin-Releasing Hormone; Male; Microinjections; Rats; Rats, Wistar; Subarachnoid Hemorrhage; Time Factors; Vasospasm, Intracranial