Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cortical blood flow of the rat brain was decreased at 44% by the bilateral occlusion of common carotid artery. The intraperitoneal injection of the leu-enkephalin before and after ischemia restored the blood flow and increased the volume of the lymph in ductus thoracicus. Cerebrovascular action of leu-enkephalin was connected with its lymphostimulating activity and vasodilation.
 ...
PMID:[Disorders of cerebral blood flow in ischemia and correction by leu-enkephalin]. 178 63

Hemodynamic responses (blood pressure, as well as cardiac output (CO), peripheral and CNS blood flow changes measured via radioactive microspheres) were analyzed in anesthetized rats 2 min following intrathecal (IT) administration (10 microliters) of either 5-ion control solution or 20 nmol of dynorphin A(1-13) into the lower thoracic space (T10-T12). Mean arterial pressure (MAP) significantly increased within 2 min following IT dynorphin A(1-13) due to rise in total peripheral resistance, whereas CO significantly declined. Two minutes post-IT-dynorphin A(1-13) administration spinal cord blood flow also significantly decreased for 2 cm anterior and 1 cm posterior from the tip of the spinal catheter, which reflected a significant elevation in tissue flow resistance of spinal cord vessels in spite of the reduction of CO. As well, tissue blood flow resistance was also increased at this time in the kidneys and adrenal glands. The results indicate that within 2 min after intrathecal dynorphin A(1-13) administration an acute increase in blood flow resistance of spinal cord vessels around the tip of the spinal catheter occurs, at a time when the animal is also hypertensive. It is suggested that the associated pressor response may, in part, be caused by dynorphin A evoking localized ischemia.
 ...
PMID:Intrathecal dynorphin A administration causes pressor responses in rats associated with an increased resistance to spinal cord blood flow. 256 52

The selective kappa opioid receptor antagonist nor-binaltorphimine (nor-BNI) was used to distinguish a kappa opioid component in the mechanisms underlying the hindlimb paralysis, ischemia, and neuronal injury induced in the rat by the kappa opioid agonist dynorphin A. Spinal intrathecal (i.t.) injection of nor-BNI (20 nmol) either 15 min or immediately before i.t. injections of 5 or 20 nmol of dynorphin A failed to alter the dynorphin A-induced disruption of hindlimb motor function and nociceptive responsiveness. Nor-BNI also did not change the 3-fold increases in cerebrospinal fluid lactate concentrations produced by 20 nmol of dynorphin A. Neuroanatomical evaluations revealed that the cell loss, fiber degeneration, and central gray necrosis in lumbosacral spinal cords of rats treated with 20 nmol of dynorphin A were not altered by nor-BNI (20 nmol, i.t.). Thus, the spinal cord injury and associated neurological deficits resulting from i.t. injection of dynorphin A appear to be primarily, if not totally, attributable to its non-kappa opioid action(s).
 ...
PMID:Dynorphin A-induced rat hindlimb paralysis and spinal cord injury are not altered by the kappa opioid antagonist nor-binaltorphimine. 257 91

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.
 ...
PMID:Opioid peptide levels in gerbil brain after transient ischemia: lasting depletion of hippocampal dynorphin. 288 47

Although endogenous opioids have been implicated in the pathophysiology of spinal cord injury and brain ischemia, the role of specific opioid peptides and opiate receptors in the pathophysiology of traumatic brain injury remains unexplored. This study examined regional changes in brain opioid immunoreactivity and cerebral blood flow (CBF) after fluid-percussion brain injury in the cat and compared the effect of an opiate antagonist (Win 44,441-3 [Win-(-)]) with its dextroisomer Win 44,441-2 [Win-(+)] (which is inactive at opiate receptors) in the treatment of brain injury. Dynorphin A immunoreactivity (Dyn A-IR) but not leucine-enkephalin-like immunoreactivity accumulated in injury regions after traumatic injury; Dyn-IR increases also occurred predominantly in those areas showing significant decreases in regional CBF. Administration of Win-(-) but not Win-(+) or saline at 15 min after injury significantly improved mean arterial pressure, electroencephalographic amplitude, and regional CBF and reduced the severity and incidence of hemorrhage. Win-(-) also significantly improved survival after brain injury. Taken together, these findings suggest that dynorphin, through actions at opiate receptors, may contribute to the pathophysiology of secondary brain injury after head trauma and indicate that selective opiate-receptor antagonists may be useful in treatment of traumatic brain injury.
 ...
PMID:Endogenous opioids may mediate secondary damage after experimental brain injury. 289 3

Changes in endogenous opioid concentrations and the effect of treatment with the opiate receptor antagonist WIN 44,441-3 (WIN) were evaluated after middle cerebral artery occlusion (MCA-O) in rats. Animals treated with WIN at doses of 0.4 to 400 micrograms/kg 15 min, 3 hr and 6 hr after MCA-O had significantly higher mean arterial blood pressure than saline controls (P less than .05). Twenty-four hours after MCA-O, WIN-treated rats had significantly greater recovery of EEG activity and higher neurological scores than the controls; these actions were greatest at a dose of 40 micrograms/kg (P less than .01). The neurological outcome correlated with recovery of the ipsilateral EEG (P less than .01). The mortality rate 24 hr after occlusion and the infarct size were not significantly different from controls. At 1 hr after MCA-O, there were no significant differences in regional concentrations of endogenous opioid peptides (dynorphin, Leu-enkephalin and beta-endorphin) between the injured and uninjured hemispheres. These are the first studies to evaluate the effects of an opiate antagonist over a wide dose range in cerebral ischemia. Dose-related beneficial actions were found with regard to several, but not all, outcome measures. The absence of regional opioid changes after regional ischemia, in contrast to previous studies of spinal cord ischemia and brain trauma, was unexpected, but may reflect limited regional and temporal sampling.
 ...
PMID:Levels of endogenous opioids and effects of an opiate antagonist during regional cerebral ischemia in rats. 320 16

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.
 ...
PMID:Time-course of neuropeptide changes in peri-ischemic zone and amygdala following focal ischemia in rats. 749 57

Perinatal hypoxic-ischemic brain injury was induced in 7- to 8-day-old rats by ligating the left carotid artery with subsequent exposure to 9% oxygen atmosphere for 2.5 h. The animals were killed 7 days later and grouped according to the degree of brain injury sustained after hypoxia-ischemia. Total protein content measured in striatum ipsilateral to the ligation, and dissected from brains showing extensive damage, was reduced to 64% of contralateral tissue. The protein content was not altered in other groups including control animals exposed to air and in sham-operated animals exposed to hypoxic conditions. The concentration of (pg/mg protein) and total (pg/striatum) striatal dynorphin A-like immunoreactivity (DLI) from brains with extensive damage were increased to 481% and 285% of the contralateral side, respectively. Hypoxia-ischemia increased striatal neuropeptide Y-like immunoreactivity (NPYLI) concentration from brains with extensive damage to 157% of contralateral side, but when the results were expressed as total NPYLI content per striatum, NPYLI content in striatum with extensive damage remained unaltered. Substance P-like immunoreactivity (SPLI) concentration and total content per striatum from brains with extensive damage were reduced to 66% and 43% of the contralateral side, respectively. D1 and D2 receptor density in animals killed 10 days after injury was reduced by 24% and 22% of control, respectively, in striatum from brains with extensive damage. These results indicate complex changes in brain neuropeptides following neonatal hypoxia-ischemia. Damage in the substance P system could have functional effects on dopaminergic transmission while the increase in NPYLI and in DLI concentrations may respectively reflect the relative preservation from neuronal damage and possibly an increase in neuropeptide synthesis or decrease in release. The decrease in SPLI concentration and the increase DLI concentration induced by hypoxia-ischemia suggests that these peptides may be present in separate neurons.
 ...
PMID:Effect of neonatal hypoxia-ischemia on nigro-striatal dopamine receptors and on striatal neuropeptide Y, dynorphin A and substance P concentrations in rats. 753 99

Involvement of the IEGs in brain injury and ischemia is under intensive investigation (Gubits et al., 1993). There are several families of the IEGs. They include the fos, jun, and zinc finger genes that encode transcription factors. Products of the fos family (c-fos, fra-1, fra-2, and fos B) bind to members of the jun family (c-jun, jun B, jun D) via leucine zippers, and this dimer then binds to the AP-1 site (consensus sequence -TGACTCA-) in the promoter of target genes, which in turn regulate the expression of late response genes that produce long-term changes in cells. For example, c-fos may regulate the long-term expression of preproenkephalin, nerve growth factor, dynorphin, vasoactive intestinal polypeptide, tyrosine hydroxylase and other genes with AP-1 sites in their promoters (Curran and Morgan, 1987; Sheng and Greenberg, 1990). It is likely that the c-fos gene up-regulation observed in ischemic astrocytes leads to the changes observed in the expressions of hsp and cytoskeleton protein genes in this experimental model. This is supported by the findings of Sarid (1991) and Pennypacker et al. (1994) who have shown that AP-1 DNA binding activity in hippocampus recognized an AP-1 sequence from the promoter region of the GFAP which is a potential target gene. van de Klundert et al. (1992) also suggested the involvement of AP-1 in transcriptional regulation of vimentin. IEGs can be induced within minutes by extracellular stimuli including transmitters, peptides, and growth factors. In this study, we have shown that c-fos induction by ischemia was rapid and transient.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Gene expression in astrocytes during and after ischemia. 756 84

Lumbar subarachnoid injection of dynorphin A causes an ischemia-induced neuronal degeneration and persistent hindlimb paralysis. The protective effects of a variety of competitive and non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists indicate that activation of the NMDA receptor complex is essential for dynorphin A-induced spinal cord injury. 1-Aminocyclopropanecarboxylic acid (ACPC) is a high affinity, partial agonist at strychnine-insensitive glycine receptors associated with the NMDA receptor complex. Pretreatment of rats with ACPC (100 and 200 mg/kg, i.p., 30 min prior to dynorphin A) significantly eliminated the persistent hindlimb motor deficits and neuropathological changes produced by 20 nmol of this peptide. The neuroprotective effects of ACPC (100 mg/kg, i.p.) were abolished by parenteral administration of glycine (800 mg/kg, 30 min prior to ACPC), consistent with other in vivo and in vitro studies indicating that the pharmacological actions of ACPC are effected through strychnine-insensitive glycine receptors. When given instead as six daily injections (200 mg/kg, i.p.) followed by an injection-free day, ACPC also significantly improved neurological recovery following dynorphin-A injection. These results support earlier indications that: (1) activation of the NMDA receptor complex plays a critical role in mediating dynorphin A-induced rat spinal cord injury; (2) ACPC provides an effective means of antagonizing excitotoxic phenomena; and (3) chronic administration of ACPC can elicit a persistent change in the NMDA receptor complex.
 ...
PMID:1-Aminocyclopropanecarboxylic acid protects against dynorphin A-induced spinal injury. 781 51


1 2 3 4 Next >>