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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endogenous opioids have been shown to produce beneficial effects in experimental stroke. To evaluate both neurophysiological and biochemical parameters, we induced massive cerebral ischemia in 11 rabbits according to the method standardized in our laboratory, using microspheres injected through the internal carotid artery. Binding studies were performed in the 11 embolized, in nine control, and in five sham-operated rabbits using the appropriate concentration of [3H]dynorphin A (1-8). Neurophysiological parameters were evaluated under baseline conditions and 1 hour after embolization, surgical preparation, or sham operation in 17 rabbits. Comparison of visual readings of the electroencephalograms and analyses of the quantified electroencephalograms under baseline conditions and after embolization indicated a marked and statistically significant (p less than 0.01) increase in bilateral delta activity; histologic examination confirmed bilateral brain edema. Binding studies on kappa-opioid receptors indicate that 1 hour after embolization there were significantly more (28%) kappa-opioid receptors (Bmax) in six embolized rabbits than in five sham-operated animals. No significant changes were observed in the affinity parameters, particularly in the dissociation constant (Kd). Our results indicate a role for endogenous dynorphin peptides in the pathogenesis of stroke.
Stroke 1990 Jun
PMID:Kappa-opioid receptor changes and neurophysiological alterations during cerebral ischemia in rabbits. 216 75

In previous studies done in our laboratory, we demonstrated that morphine sulfate could depress heart rate and cardiac output when added to the perfusate of a working rat heart model using a modified Langendorff preparation. In this study we investigated three different delta agonists and a mu agonist by adding each to the perfusate in a fashion similar to the experiments done with morphine sulfate. We found that all three delta agonists, leu-enkephalin, D-ala-D-leu-enkephalin (DADL), and D-Pen enkephalin, would significantly decrease cardiac output. In the case of D-Pen enkephalin, heart rate and stroke volume were also significantly decreased. Additionally the mu agonist Tyr-D-ala-gly-N-met-phe-gly-ol (DAGO) also caused a significant decrease in heart rate, cardiac output, and stroke volume. The data suggest that all three delta agonists and DAGO are capable of depressing heart rate, cardiac output, and stroke volume at concentrations between 10(3) and 10(4) lower than those used in studies with morphine sulfate.
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PMID:Delta and Mu receptor agonists correlate with greater depression of cardiac function than morphine sulfate in perfused rat hearts. 253 20

Opiate antagonists, including receptor antagonists and physiologic antagonists, have been shown to produce beneficial effects in a variety of models of CNS injury and in a variety of species. Opiate antagonists improve spinal cord blood flow, electrical conduction of the spinal cord, pathological changes, and motor recovery following traumatic spinal cord injury in cats. TRH appears to be superior to naloxone in this regard, although direct comparisons between receptor-selective opiate receptor antagonists and TRH have not been made. Similarly, opiate antagonists are effective in improving outcome and reducing pathological changes following ischemic spinal cord injury in rabbits. Beneficial effects for opiate receptor antagonists have also been observed after fluid percussion head injury in cats. Effects of opiate antagonists in the treatment of experimental stroke have been more controversial, although the weight of evidence supports a therapeutic effect in various models and species. Following spinal cord injury, best evidence suggests that pathophysiological responses produced by opioids may be mediated by the dynorphin opioid system and/or the kappa opiate receptor. This issue is of considerable importance, since it may lead to the development of more effective and specific forms of therapy. The role of specific opioid systems and specific opiate receptors in traumatic head injury or cerebral ischemia have not been adequately studied and should be the subject of future investigation. A number of controlled clinical studies are now either planned or under way to investigate the potential therapeutic effects of naloxone and TRH in CNS injury. Data from these studies should be available within the next several years.
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PMID:Role of thyrotropin-releasing hormone and opiate receptor antagonists in limiting central nervous system injury. 283 Jul 71

Peptides derived from each of the 3 endogenous opioid precursors were measured in gerbil brain regions at various times after transient bilateral carotid artery occlusion using radioimmunoassays specific for beta-endorphin-, met-enkephalin-, and dynorphin A-related peptides. Lasting changes were observed only in the hippocampus. The most striking effect was on dynorphin A immunoreactivity, which was reduced by 30-40% as early as 1 hour after recirculation and remained at 50% of the control level for at least 1 week. In some experiments dynorphin levels showed a transient recovery at 24 hours. These results demonstrate a unique sensitivity of the dynorphin-containing dentate granule cell-mossy fiber pathway to transient ischemia. Although these cells remain histologically intact, the decrease in dynorphin level precedes and continues during the delayed loss of hippocampal CA1 neurons characteristic of this model and further defines the selective vulnerability of hippocampal circuitry following ischemia. These observations clearly identify the hippocampus as a well-defined brain region in which further studies of the postischemic pathophysiology of endogenous opioid peptides may provide a rational basis for evaluating the place of opiate pharmacology in stroke treatment.
Stroke
PMID:Opioid peptide levels in gerbil brain after transient ischemia: lasting depletion of hippocampal dynorphin. 288 47

Previously, using a middle cerebral artery occlusion model in Wistar rat, we showed autonomic disturbances similar to those seen clinically and observed striking neurochemical changes in cortical and subcortical sites at 5 days following stroke. The neurochemical changes may account for functional recovery and/or autonomic disturbances after focal ischemia. To understand the possible mechanisms and to facilitate future studies, it is necessary to define the time-courses of these changes. Using immunohistochemical staining with the peroxidase-antiperoxidase reaction, the changes in several neuropeptides over the peri-ischemic region and the ipsilateral central and basolateral nucleus of the amygdala were investigated at different times after middle cerebral artery occlusion. In the experimental group, neuropeptide Y immunoreactivity appeared to increase by 6 hours in the peri-ischemic region. Using image analysis to quantify the staining intensity, the change became statistically significant at 1 day, peaked around 3 days, and subsided at 10 days. There was a delayed increase in neuropeptide Y in the ipsilateral basolateral nucleus of the amygdala with a peak around 3 days. Immunoreactive staining for leucine-enkephalin, dynorphin, and neurotensin demonstrated an increase that was localized to the ipsilateral central nucleus of the amygdala with a peak around 3 days and a return to baseline levels by 10 days. The results support a specific time-course for each of the neuropeptides studied and indicate that a survival time of 3 days after focal ischemia is the critical period for examining the relationship between neuropeptide responses and neuronal or functional recovery.
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PMID:Time-course of neuropeptide changes in peri-ischemic zone and amygdala following focal ischemia in rats. 749 57

The evidence indicating that the insular cortex is a likely candidate to mediate stress-induced cardiovascular responses is reviewed. Both neuroanatomical and electrophysiological investigations demonstrate that the insular cortex receives an organized representation of visceral information. In addition, the insular cortex also receives highly processed association cortex information. The insular cortex is also highly interconnected with many subcortical limbic and autonomic regions. This combination of sensory input and limbic/autonomic connectivity would be necessary to permit the insular cortex to be a critical site for the integration of emotional and autonomic responses. Stimulation of the insular cortex elicits specific cardiovascular and autonomic responses from discrete sites. Phasic stimulation entrained to the cardiac cycle is even capable of causing severe arrhythmias. The efferent pathways and some of the neurotransmitter mechanisms have determined. It appears that the lateral hypothalamic area is the primary site of synapse for responses originating in the insular cortex and this information is relayed by NMDA glutamatergic receptors and modulated by neuropeptides including neuropeptide Y, neurotensin, leu-enkephalin and dynorphin. Finally, a rat stroke model, which includes the insular cortex in the infarct region indicates that disruption of the insula can produce substantial cardiac and autonomic abnormalities, which might be similar to those produced by stress. Some of the chronic neurochemical changes, including increases in opioids, neuropeptide Y and neurotensin in the central nucleus of the amygdala, which might be mediating these cardiovascular disturbances, have been determined.
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PMID:Identification of a cortical site for stress-induced cardiovascular dysfunction. 769 33

We studied the effect of dynorphin A-(1-13), dynorphin A-(1-17), des-tyr dynorphin A-(2-17) (inactive at opioid receptor) or normal saline (NS) microinjected into the paraventricular nucleus (PVN) (n = 9/treatment) on mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), stroke volume (SV), and left ventricular stroke work (LVSW) during fixed-volume hemorrhage in conscious rats. Microinjection of dynorphin A-(1-13) (6 nmol) into PVN at 15 min following the termination of fixed volume hemorrhage (8 ml/300 g) significantly decreased MAP from 50 min to 2 hr postinjection (P < 0.05 compared to animals receiving NS), while dynorphin A-(1-17) (6 nmol) significantly decreased MAP from 30 min up to 2 hr postinjection (P < 0.05). Microinjection of des-tyr dynorphin A-(2-17) (6 nmol) into the PVN did not significantly affect MAP following hemorrhage. Recovery of MAP in the dynorphin A-(1-13) and dynorphin A-(1-17) groups following hemorrhage was found to be significantly attenuated compared to the NS group (P < 0.05 and P < 0.01, respectively). Dynorphin A-(1-13) increased heart rate at 20 min and decreased stroke volume at 60 min after microinjection directly into the PVN following hemorrhage when compared with the NS group (P < 0.05). Both dynorphin A-(1-13) and dynorphin A-(1-17) significantly decreased LVSW after PVN injection following hemorrhage compared to NS group (both P < 0.05). No significant effects were observed on CO following microinjection of active or inactive opioid peptides into the PVN following hemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of dynorphin microinjection in the paraventricular nucleus on the hemodynamic response to hemorrhage in the rat. 791 78

The region surrounding the anteroventral part of the third ventricle (AV3V) is important for the regulation of cardiovascular homeostasis. In the present study we investigated the effect of the kappa-opioid receptor agonists dynorphin A-(1-17) and dynorphin A-(1-13) microinjected into the AV3V region on mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), stroke volume (SV), and left ventricular stroke work (LVSW) during fixed-volume hemorrhage in conscious rats. During fixed-volume hemorrhage (8 ml/300 g), dynorphin A-(1-17) (6 nmol), microinjected into the AV3V, significantly decreased MAP up to 30 min postinjection (P < 0.05). Recovery of MAP, SV, and LVSW in the dynorphin A-(1-17) group following hemorrhage was found to be significantly attenuated compared to that in animals receiving microinjection of normal saline (NS) vehicle into the AV3V (P < 0.05). Hypothalamic microinjection of dynorphin A-(1-13) (6 nmol) also attenuated the recovery of SV following hemorrhage compared with the NS group (P < 0.05). No significant effects were observed on HR or CO following microinjection of dynorphin into the AV3V region. The results of this study suggest that activation of the kappa-opiate receptor system in the AV3V region of the hypothalamus can attenuate the compensatory cardiovascular responses to hemorrhage.
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PMID:Effect of dynorphin microinjection in the anterior hypothalamus (AV3V) region on the hemodynamic response to hemorrhage in the rat. 809 73

The nucleus of the solitary tract (NTS) is important for the regulation of cardiovascular homeostasis. In the present study we investigated the effect of dynorphin A-(1-13), dynorphin A-(1-17) and dynorphin A-(2-17) microinjected into the NTS on mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), stroke volume (SV) and left ventricular stroke work (LVSW) following hemorrhage in conscious rats. Following fixed-volume hemorrhage (8 ml/300 g), microinjection of dynorphin A-(2-17) (6 nmol), which is inactive at opioid receptors, into the NTS significantly attenuated the recovery of CO, SV and LVSW following hemorrhage when compared to those animals receiving a microinjection of normal saline (NS) vehicle into the NTS (P < 0.01). NTS microinjection of dynorphin A-(2-17) also increased HR following hemorrhage when compared with the NS group (P < 0.05). No significant effects were observed on CO, SV and LVSW following NTS microinjection of the kappa-opioid agonists, dynorphin A-(1-13) and dynorphin A-(1-17), although dynorphin A-(1-13) microinjection increased HR following hemorrhage when compared with control animals (P < 0.05). Microinjection of all three peptide fragments had no significant effect on MAP when compared with MAP of the control group following hemorrhage. The results of this study suggest that dynorphin A-(2-17) in the NTS can attenuate the compensatory cardiovascular responses to hemorrhage, perhaps via a non-opioid mechanism.
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PMID:Cardiovascular effects of microinjection of dynorphin fragments into the nucleus of the solitary tract (NTS) are mediated by non-opioid mechanisms. 810 18

We have developed a stroke model involving middle cerebral artery occlusion in the rat which elicits changes in cardiac and autonomic variables that are similar to those observed clinically. It is likely that these neurogenic autonomic responses are mediated by changes in neurotransmitter systems subsequent to the stroke. This possibility was investigated by examining changes in immunohistochemical staining for tyrosine hydroxylase, neuropeptide Y, leu-enkephalin, neurotoxins and dynorphin following middle cerebral artery occlusion in the rat. Computerized image analysis was used to provide semi-quantitative measurements of the changes. The ischemic region was centered primarily in the insular cortex. The results indicate that there are significant increases in immunostaining for tyrosine hydroxylase and neuropeptide Y in the insular cortex within the peri-infarct region. Neuropeptide Y staining was also significantly increased in the basolateral nucleus of the amygdala, ipsilateral to the middle cerebral artery occlusion, which did not appear to be included in the infarct. Leu-enkephalin, neurotensin and dynorphin staining was significantly elevated in the central nucleus of the amygdala ipsilateral to the occlusion of the middle cerebral artery. These neurochemical changes are discussed as possible mechanisms mediating the cardiac and autonomic consequences of stroke or as part of a process to provide neuro-protection following focal cerebral ischemia.
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PMID:Neurochemical changes following occlusion of the middle cerebral artery in rats. 854 80


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