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)

We examined the effect of lidocaine on ischemic neuronal injury in the rat forebrain ischemia model. Cerebral ischemia was achieved with bilateral carotid artery occlusion and controlled hypotension to a mean of 50 torr for 10 minutes. Perfusion-fixation was performed 7 days after ischemia, subsequent to which the brains were sectioned coronally and stained with hematoxylin and eosin. Ischemic neuronal injury was quantitatively expressed (after direct counting) as a percentage of total neurons, that is, ischemic neurons divided by (ischemic neurons + normal neurons). Predictably, the selectively vulnerable hippocampal areas exhibited the most marked neuronal injury. In the CA1/CA2 sectors, lidocaine-treated rats demonstrated less injury (34 +/- 14%) than untreated (64 +/- 9%) or saline-treated (70 +/- 10%) rats. However, these superficially pronounced numerical differences were not of statistical significance (p greater than 0.05). In the CA3 sector, neuronal injury in lidocaine-treated rats (31 +/- 14%) was significantly different at p less than 0.05 from the untreated (80 +/- 5%) but not the saline-treated (59 +/- 13%) group. We conclude that lidocaine may have an only marginal beneficial effect on forebrain ischemia in rats.
 ...
PMID:Effect of lidocaine on forebrain ischemia in rats. 291 25

The effects of mannitol, nimodipine, and indomethacin on ischemic neuronal injury were examined in 45 rats divided equally into nine groups subjected to 10 minutes of forebrain ischemia. Of two control groups, one received maintenance fluids while the other received a normal saline bolus. In the remaining seven groups, mannitol, nimodipine, and indomethacin were administered singly or in combination 5 minutes before forebrain ischemia. Seven days after ischemia, the brains were perfusion-fixed, sectioned coronally into 2.8-mm slices, and stained with hematoxylin and eosin. Ischemic neurons were directly counted on predetermined regions of standardized serial sections. Considerable amelioration of ischemic injury (ischemic neurons/total neurons) was observed with mannitol (ischemic injury, 7 +/- 5% in the hippocampal CA1/CA2 sectors and 28 +/- 17% in the CA3 sector). This is in contrast to control values of 64 +/- 11% and 80 +/- 6%, respectively, and those obtained in the normal saline group of 70 +/- 10% and 59 +/- 13%, respectively. The beneficial effect with nimodipine reached significance in only the hippocampal CA3 sector (ischemic injury, 35 +/- 21%). Indomethacin showed no significant benefit. Combining the agents resulted in significantly reduced neuronal injury compared with control groups, although the effect was not greater than that achieved with mannitol alone. The degree of ischemic injury was least when all three agents were used in combination (ischemic injury, 12 +/- 12% in the hippocampal CA1/CA2 sectors and 4 +/- 4% in the CA3 sector). Our data support the concept that successfully blocking the ischemic cascade with a single, diversely acting agent or multiple agents will evoke the best beneficial response.
 ...
PMID:Effect of mannitol, nimodipine, and indomethacin singly or in combination on cerebral ischemia in rats. 312 27

We investigated progression and recovery of neuronal damage during and after global cerebral ischemia in gerbils after bilateral occlusion of the common carotid arteries, using the immunohistochemical method (reaction for tubulin and creatine kinase BB-isoenzyme). The earliest, but reversible, ischemic lesions occurred after 3 minutes' ischemia in the subiculum-CA1 and CA2 regions of the hippocampus. The lesions became irreversible after 4 minutes' ischemia. The ischemic and postischemic lesions in the cerebral cortex, thalamus, and caudoputamen were partially or completely reversible if the ischemic period was 5 minutes, whereas delayed degeneration occurred in the pyramidal cells of the medial CA1 region after reperfusion for 48 hours (delayed neuronal death). After 10 minutes' ischemia and subsequent reperfusion, delayed neuronal death extended from the medial to the lateral CA1 region; the ischemic and postischemic lesions in the cerebral cortex, thalamus, and caudoputamen also expanded during reperfusion. Our investigation demonstrates that selective vulnerability existed in global cerebral ischemia as in incomplete or regional ischemia and suggests that neurons in many areas of the brain possessed the potential for recovery, progressive deterioration, and even delayed neuronal death depending on the severity and duration of cerebral ischemia.
 ...
PMID:Immunohistochemical investigation of ischemic and postischemic damage after bilateral carotid occlusion in gerbils. 320 12

The selective vulnerability of pyramidal neurons in the CA1 hippocampal region in ischemic rat brain may be preceded by regional alterations of energy metabolism during early reperfusion. We measured ATP, phosphocreatine (PCr), and glucose in paramedian and lateral CA1 and in an area showing little postischemic cell loss, CA2. ATP levels in paramedian CA1 were depressed immediately after 30 min of ischemia (P less than or equal to 0.02) and remained abnormal after 2 hr of reperfusion (P less than or equal to 0.05). PCr was reduced substantially in both subdivisions of CA1 immediately after ischemia (P less than or equal to 0.04) but returned to normal levels after 2 hr. Glucose levels were depressed in paramedian CA1 and CA2 after ischemia (P less than or equal to 0.02) but corrected with reperfusion. We determined approximately P, the sum of ATP and PCr, in separate experiments investigating regional differences in consumption of high-energy phosphate metabolites during complete ischemia. The approximately P levels of rats subjected to 30 min of reversible ischemia followed by 2 hr of reperfusion showed a different pattern of regional differences from those seen in sham-ischemic animals (P less than or equal to 0.01), indicating a persistent depression of metabolic rate in CA1 during reperfusion. We conclude that regional depletion of high-energy phosphates and alteration of metabolic rate may contribute to the selective vulnerability of the CA1 region during brain ischemia.
 ...
PMID:Regional depletion of adenosine triphosphate, phosphocreatine, and glucose in ischemic hippocampus. 322 10

Mongolian gerbils were exposed to 15 min of cerebral ischemia. Quantitative histology was used to establish neuronal damage in the CA1, CA2/3, and CA3 sectors of the hippocampus 2 weeks after the insult. Seven moribund animals were sacrificed earlier to examine whether there is a correlation between hippocampal damage and mortality. Surviving animals had a 86.6% loss of CA1 neurons. In the CA2/3 and CA3 sectors 62.7 and 72.6% of the neurons were preserved. Moribund animals had a further dramatic loss of nerve cells in these sectors, to 14.8 and 20.3%, respectively. The reduction of CA2/3 neurons and survival time were correlated. In addition, gerbils which would later become moribund were found to have a significant increase in plasma osmolarity from 319 to 342 mosm/liter and of hematocrit from 47.4 to 53.9 at day 4 after ischemia.
 ...
PMID:Determinants of survival after forebrain ischemia in Mongolian gerbils. 324 2

The neuroprotective effects of MK-801, a noncompetitive antagonist of N-methyl-D-aspartate (NMDA) receptors, were evaluated in models of cerebral ischemia using Mongolian gerbils. Bilateral occlusion of the carotid arteries for a period of 5 min resulted in a consistent pattern of degeneration of hippocampal CA1 and CA2 pyramidal neurons, which was quantified using an image analyzer. Systemic administration of MK-801 (0.01-10 mg/kg, i.p.) 1 hr prior to the occlusion caused a dose-dependent protection of the CA1 and CA2 neurons. The ED50 value for neuroprotection by MK-801 was calculated to be 0.3 mg/kg, and at doses greater than or equal to 3 mg/kg the majority of animals were completely protected against the ischemic insult. Systemic administration of MK-801 (1 or 10 mg/kg, i.p.) 1 hr prior to unilateral occlusion of the right carotid artery resulted in significant protection against hippocampal neurodegeneration following 10 min of occlusion, and increased the survival rate after 30 min of occlusion. The potent neuroprotective effects of MK-801 in these cerebral ischemia models add further weight to the evidence that NMDA receptors are involved in the mechanism of ischemia-induced neuronal degeneration.
 ...
PMID:Systemic administration of MK-801 protects against ischemia-induced hippocampal neurodegeneration in the gerbil. 331 11

Following brief ischemia, the Mongolian gerbil is reported to develop unusual hippocampal cell injury (Brain Res 239:57--69, 1982). To further clarify this hippocampal vulnerability, gerbils were subjected to ischemia for 3, 5, 10, 20, and 30 min by bilateral occlusion of the common carotid arteries. They were perfusion-fixed after varying intervals of survival time ranging from 3 h up to 7 days. Following brief ischemia (5--10 min), about 90% of the animals developed typical hippocampal damage. The lesion was present throughout the extent of the dorsal hippocampus, whereas damage outside the hippocampus was not observed. Each sector of the hippocampus showed different types of cell reaction to ischemia. Ischemia cell change was seen in scattered CA4 neurons , and reactive change was found in CA2, whereas CA1 pyramidal cells developed a strikingly slow cell death process. Ischemia for 3 min did not produce hippocampal lesion in most cases. Following prolonged ischemia (20--30 min), brain injury had a wide variety in its extent and distribution. These results revealed that the gerbil brief ischemia model can serve as an excellent, reliable model to study the long-known hippocampal selective vulnerability to ischemia. Delayed neuronal death in CA1 pyramidal cells was confirmed after varying degrees of ischemic insult. These findings demonstrated that the pathology of neuronal injury following brief ischemia was by no means uniform nor simple.
 ...
PMID:Selective vulnerability in the gerbil hippocampus following transient ischemia. 669 54

In the CA1 subfield of the gerbil hippocampus, an unusual series of changes were noticed after ischemia. Mongolian gerbils were subjected to bilateral carotid occlusion for 5 min. Perfusion fixation was performed 3, 6 and 12 h or 1, 2, 4, 7 and 21 days afterwards. Specimens obtained from the dorsal hippocampus were processed for light and electron microscopy. Three different types of changes were observed in the CA4, CA2 and CA1 subfields. In CA4, the change was rapid and corresponded to ischemic cell change. The alteration in CA2 was relatively slow, and identical to what has been called reactive change. On the contrary, the change in the CA1 pyramidal cells was very slow, only becoming apparent by light microscopy 2 days following ischemia. The CA1 subfield was selected for electron microscopic observation. The lamellar alignment of proliferated cisterns of the endoplasmic reticulum was the most conspicuous finding in these cells. Four days following ischemia, almost all of the pyramidal cells in CA1 were destroyed. In the CA1 neuropil, numerous presynaptic terminals remained without being apposed to normal postsynaptic sites. These changes in CA1, called here 'delayed neuronal death', may differ from those thought to be typical of ischemic neuronal damage. It was unlikely that the disturbance of local blood vessels was the cause of these changes.
 ...
PMID:Delayed neuronal death in the gerbil hippocampus following ischemia. 709 91

Nitric oxide can act as a neurotransmitter and a retrograde modulator of synaptic transmission, but uncontrolled nitric oxide synthase activity has been associated with neural degeneration. Although earlier studies using immunohistochemistry, in situ hybridization, and NADPH-diaphorase staining had suggested that nitric oxide synthase is not expressed in the CA1 neurons of the hippocampus, we have recently demonstrated that NADPH-diaphorase activity can be detected in CA1 neurons of the hippocampus. To confirm that this diaphorase activity reflects nitric oxide synthase, we have developed a more sensitive in situ hybridization procedure, and an RNase protection assay to detect message for constitutive nitric oxide synthase, the form constitutively expressed in many neurons. Message for constitutive nitric oxide synthase is expressed in the hippocampus, and it is localized to neural cell layers CA1, CA3, the dentate gyrus and some displaced neurons, but not to CA2. Expression of constitutive nitric oxide synthase message in the CA1 region was lost when pyramidal neurons died due to transient forebrain ischemia, supporting the conclusion that CA1 pyramidal cells express constitutive nitric oxide synthase. Although constitutive nitric oxide synthase message is strongly expressed in CA3 and the dentate gyrus, there is little diaphorase activity in these cells, suggesting that there may be post-transcriptional controls that limit constitutive nitric oxide synthase expression in some cells. Message for constitutive nitric oxide synthase is also present in a number of other regions, including the amygdala, several hypothalamic nuclei, the cerebellum, the olfactory bulb, two distinct regions of the perirhinal cortex, the subthalamic nuclei, a neuronal layer in the retrosplenial granular cortex, the lateral geniculate nucleus, the presubiculum, the inferior colliculus, the superior colliculus, the pedunculopontine tegmental nucleus, and scattered individual neurons in the cortex, hippocampus and brainstem. These studies support a role for nitric oxide in multiple regions of the central nervous system. In particular, nitric oxide synthase, the enzyme responsible for the synthesis of nitric oxide, is expressed in the CA1 region of the hippocampus, where there is evidence that nitric oxide may play a major role in long-term potentiation. CA1 hippocampal neurons are an example of a population of neurons that express constitutive nitric oxide synthase but are very sensitive to excitotoxicity and ischemic insults.
 ...
PMID:Expression of the neural form of nitric oxide synthase by CA1 hippocampal neurons and other central nervous system neurons. 753 83

The influence of prolonged postischemic hyperventilation was studied in the model of global brain ischemia produced by 15 min cardiac arrest in dogs with 8 h recirculation. Histopathological examination of neuronal damage using silver impregnation showed the presence of numerous heavy argyrophylic neurons in the striatum and CA2 hippocampal subfield after 8 h of normoxic reperfusion. In dogs with prolonged 8 h postischemic hyperventilation a reduction in the occurrence of argyrophylic neurons in the striatum and their significant decrease in the hippocampal area were found. Electron microscopic study was performed to characterize the effect of respiratory alkalosis on the ultrastructural changes in neurons and correlate them with the results of silver impregnation. Ultrastructural analysis after the cardiac arrest without recirculation did not reveal the presence of dark neurons within the striatal and hippocampal areas. Neuronal alterations included a decrease in endoplasmic reticulum, mitochondrial swelling and a mild chromatin clumping. After 8 h of normoxic reperfusion many dark, shrinked neurons containing perinuclear clusters of clear vesicles were found. In hyperventilated animals the occurrence of dark neurons with extensive perineuronal edema was substantially reduced in the CA2 subfield. The effect of hyperventilation on postischemic calcium overload is discussed.
 ...
PMID:Effect of prolonged hyperventilation on ischemic injury of neurons after global brain ischemia in the dog. 756 Sep 2


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>