beta-endorphin and Brain-Ischemia

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

To explore the main pathogenic factors in the development of neuronal death during normothermic reperfusion in rabbits.. Ninety-six New Zealand rabbits were randomly allocated into two groups: group I served as non-ischemic controls; group II served as postischemic normothermic reperfusion models. Complete cerebral ischemia was induced by the four-vessel model for 30 minutes. After ischemia, rabbits in group II were further divided into three subgroups according to the duration of reperfusion: subgroup A, 30 minutes; subgroup B, 180 minutes and subgroup C, 360 minutes. Twenty-eight biochemical parameters in the brain were measured, and neuronal changes were observed by histomorphological assessment. Neurons of 12 regions were differentiated into four types: type A (normal), type B (mildly damaged), type C (severely damaged) and type D (necrotic). Bivariate correlate analysis between the levels of biochemical parameters and the percentages of each type of neurons was carried out.. The main parameters involved in the progressive decrement of type A neurons were VIP, beta-EP, PGI2, T3, T4 and Na+, K(+)-ATPase; in the increment of type B were beta-EP and TXB2; in the increment of type C were GLU and TXB2/PGI2 respectively; in the stepwise increment of percentages of type D neurons were T4, Na+, K(+)-ATPase, GLU, T3 and VIP (P < 0.05).. The main factors involved in the development of neuronal death during postischemic normothermic reperfusion in rabbits include hypermetabolism, deactivation of Na+, K(+)-ATPase, release of excitatory amino acids and disorder of neuropeptides.

Topics: Animals; beta-Endorphin; Brain Ischemia; Cell Death; Female; Male; Neurons; Rabbits; Random Allocation; Reperfusion Injury; Sodium-Potassium-Exchanging ATPase; Thromboxane B2; Vasoactive Intestinal Peptide

Topics: Animals; Asteraceae; beta-Endorphin; Brain; Brain Ischemia; Carotid Artery, Common; Drugs, Chinese Herbal; Ligation; Male; Rats; Rats, Sprague-Dawley

Abnormalities of hypothalamo-pituitary-adrenocortical axis function have been observed frequently in stroke patients. The aim of this study was to investigate plasma beta-endorphin and cortisol 24-hour secretory patterns in patients early after stroke and in the convalescent period to evaluate a possible influence of brain damage on hormonal circadian pattern.. Patients (n = 15; age, 46 to 75 years) were evaluated in the first 24 hours and 10 days after hospital admission for ischemic cerebral stroke and compared with 15 age- and sex-matched normal subjects. Blood samples for beta-endorphin and cortisol determination were drawn every 4 hours from 8 AM to 8 PM and every 2 hours from midnight to 6 AM.. Mean 24-hour beta-endorphin and cortisol levels, recorded in the acute phase, were significantly (P < .05) higher than those recorded in normal subjects; circadian rhythm was not demonstrable for either hormone. In the convalescent period, plasma cortisol 24-hour mean values and circadian rhythm returned to the normal range, whereas the plasma beta-endorphin 24-hour mean values and circadian rhythm did not.. Cerebral stroke induces abnormalities of beta-endorphin and cortisol circadian secretion. Whereas cortisol abnormalities are transient, those of beta-endorphin last longer. The dissociation between beta-endorphin and cortisol 24-hour secretory patterns might potentially serve as a marker of psychoneurological abnormalities occurring after stroke.

Topics: Aged; beta-Endorphin; Brain Ischemia; Cerebrovascular Disorders; Circadian Rhythm; Convalescence; Female; Humans; Hydrocortisone; Male; Middle Aged

The Na(+)-K(+)-adenosine triphosphatase (Na(+)-K(+)-ATPase) activity and beta-endorphin immunoreactivity were determined in rat brain at the acute stage of ischemia produced by unilateral occlusion of the middle cerebral artery (MCA). The effect of pretreatment with naloxone on these activities was also evaluated in the same model. After MCA occlusion, Na(+)-K(+)-ATPase activity was promptly reduced in the ischemic hemisphere and remained at a lower level than in the contralateral hemisphere during 90 minutes of ischemia. A single intraperitoneal 0.5-mg injection of naloxone prior to MCA occlusion attenuated the inactivation. On the other hand, beta-endorphin immunoreactivity was significantly increased following ischemia. The increase was marked in the ischemic hemisphere and was also observed in the contralateral hemisphere; this increase was not affected by the administration of naloxone. These results indicate the possibility that naloxone contributes to protecting the brain from ischemia through stabilizing the cellular membrane. The possible mechanism by which naloxone attenuates the inactivation of Na(+)-K(+)-ATPase in the ischemic brain is discussed in view of alterations of the central beta-endorphin system during ischemia.

Topics: Acute Disease; Animals; beta-Endorphin; Brain; Brain Ischemia; Male; Naloxone; Radioimmunoassay; Rats; Rats, Inbred Strains; Sodium-Potassium-Exchanging ATPase

Plasma and CSF beta-endorphin (beta-EP), beta-lipotropin (beta-LPH) and ACTH levels were studied in a group of 25 patients who underwent reversible ischaemic attacks or completed strokes. CSF beta-EP and beta-LPH in ischaemic patients were higher than those of the control population, independently of both clinical reversibility of the cerebral damage, and the time lapse sampling and the acute event. The presence of a CT demonstrable lesion was related to the highest CSF beta-EP levels. These data confirm an involvement of central opioid substances in the phenomena related to brain ischaemia. ACTH levels in the CSF did not differ from the controls; this finding further supports the concept of an independent central secretion of the different pro-opiomelanocortin-related peptides. The peripheral plasma concentrations of beta-EP, beta-LPH and ACTH, were, in contrast, within the normal range, confirming that CSF and plasma contents of pro-opiomelanocortin-related peptides are differently controlled and originate from different sources.

Topics: Adrenocorticotropic Hormone; Adult; Aged; beta-Endorphin; beta-Lipotropin; Brain Ischemia; Endorphins; Female; Humans; Ischemic Attack, Transient; Male; Middle Aged

Endorphins have been implicated in the pathophysiology of both spinal cord injury and cerebral ischemia. This review examines the nature of the experimental evidence to support this hypothesis. Present studies suggest that naloxone administration improves neurological function and outcome in the setting of the spinal cord trauma by centrally inhibiting an opiate receptor-mediated diminution of spinal cord flow. In the setting of spinal shock, naloxone administration is associated with improvement in vital sign and cardiovascular parameters as measured by mean arterial pressure, cardiac output, body temperature, and ventilation. Experiments using a variety of animal stroke models similarly support the notion that naloxone improves neurological function in the setting of cerebral ischemia by a stereospecific opiate receptor-mediated effect, but this improvement does not seem to be accompanied by augmentation of blood flow to affected areas of the brain or by any improvement in vital signs or cardiovascular parameters as seen in spinal cord trauma. A variety of mechanisms are discussed to explain these observations. The therapeutic implications of administering opiate agonists and antagonists in the setting of neurological deficits are outlined for the neurosurgeon.

Topics: Animals; beta-Endorphin; Brain Ischemia; Cats; Cerebral Infarction; Cerebrovascular Circulation; Endorphins; Evoked Potentials, Somatosensory; Hemodynamics; Naloxone; Rats; Receptors, Opioid; Respiration; Spinal Cord; Spinal Cord Injuries