Expression of zinc finger immediate early genes in rat brain after permanent middle cerebral artery occlusion.

The prolonged expression of the leucine zipper fos/jun immediate early genes (IEG) has been correlated with neuronal death after cerebral ischemia. In this study, the expression of six zinc finger IEG was examined using in situ hybridization in adult rats after middle cerebral artery occlusion (MCAO) with the suture model. NGFI-A, NGFI-B, NGFI-C, egr-2, egr-3, and Nurr1 mRNA were all induced throughout the ipsilateral cortex at 1 hour to 12 hours after MCAO.

Induction of heat-shock protein (HSP72) in the cingulate and retrosplenial cortex by drugs that antagonize the effects of excitatory amino acids.

To address the issue of the cytotoxicity of glutamate antagonists, we administered representative agents to rats and used HSP72 immunocytochemistry as a measure of neuronal injury in the brain. The doses studied spanned the reported neuroprotective range for each compound. Some, but not all, glutamate antagonists induce neuronal injury in the brain.

Skin appendage involvement in anal intraepithelial neoplasia.

Background: High-grade anal intraepithelial neoplasia (AIN III) may be premalignant. Surgical excision of large areas of anal epithelium carries significant morbidity. Ablation treatments may carry less morbidity; however, the depth of ablation is uncertain and failure to ablate dysplasia in hair shafts and other skin appendages may lead to early recurrence.

Effects of neuroprotective dose of fructose-1,6-bisphosphate on hypoxia-induced expression of c-fos and hsp70 mRNA in neonatal rat cerebrocortical slices.

In situ hybridization (ISH) measurements of c-fos and hsp70 expression were made in brain slice studies of hypoxia, with or without fructose-1,6-bisphosphate (FBP) pretreatment. Each experiment used eighty 350 microns thick cerebrocortical slices, obtained from twenty 7-day old rats. Thirty minute periods of hypoxia were followed by 8 h of hyperoxic perfusion.

DNA fragmentation and Prolonged expression of c-fos, c-jun, and hsp70 in kainic acid-induced neuronal cell death in transgenic mice overexpressing human CuZn-superoxide dismutase.

Kainic acid (KA) neurotoxicity was examined in transgenic (Tg) mice overexpressing human CuZn-superoxide dismutase (SOD-1). The doses of KA required to produce seizures, the severity of the seizures, and the regions damaged were similar in SOD-1 Tg and non-transgenic wild-type mice. Intraperitoneal KA injection induced seizure-related neuronal damage in the CA3 and CA1 regions of the hippocampus and in other regions of the brain in both SOD-1 Tg and wild-type mice.

Blood-brain barrier disruption, HSP70 expression and apoptosis due to 3-nitropropionic acid, a mitochondrial toxin.

3-Nitropropionic acid (3-NP), a mitochondrial toxin, induces apoptosis in the striatum. We wanted to determine if there was a relationship between mitochondrial dysfunction, disruption of the blood-brain barrier (BBB), and apoptosis. BBB disruption following intrastriatal injection of 3-NP was assessed by Evans blue leakage, brain water content, and by the expression of the 70 kDa heat shock protein (HSP70) and mRNA.

Heme oxygenase-1 and heat shock protein 70 induction in glia and neurons throughout rat brain after experimental intracerebral hemorrhage.

Objective: Current experimental evidence demonstrates the development of ischemic regions adjacent to and spatially remote from an intracerebral hematoma. The cause of this ischemia is uncertain. Because ischemia is a known inducer of stress genes, we investigated the induction of two stress proteins, heme oxygenase (HO)-1 and heat shock protein (Hsp) 70, after intracerebral hemorrhage in the rat.

Methylmalonyl-CoA mutase induction by cerebral ischemia and neurotoxicity of the mitochondrial toxin methylmalonic acid.

Differential screening of gerbil brain hippocampal cDNA libraries was used to search for genes expressed in ischemic, but not normal, brain. The methylmalonyl-CoA mutase (MCM) cDNA was highly expressed after ischemia and showed a 95% similarity to mouse and 91% similarity to the human MCM cDNAs. Transient global ischemia induced a fourfold increase in MCM mRNA on Northern blots from both hippocampus and whole forebrain.

Global ischemia induces apoptosis-associated genes in hippocampus.

Using in situ hybridization, Northern blotting and RT-PCR we studied the post-ischemic expression of bcl-2, bcl-x, bax and ICE. One day following 5 min or 10 min of global ischemia bcl-2 and bcl-x mRNAs were induced in CA1 hippocampal pyramidal neurons while bax was unchanged. By 72 h after ischemia the expression of bcl-2, bcl-x and bax mRNAs decreased in CA1.

DNA fragmentation and HSP70 protein induction in hippocampus and cortex occurs in separate neurons following permanent middle cerebral artery occlusions.

DNA nick end-labeling (TUNEL) and heat shock protein (HSP)70 immunocytochemistry were performed on the same brain sections 1 (n = 6), 3 (n = 12), and 7 (n = 7) days following permanent middle cerebral artery (MCA) occlusions produced in adult rats using the endovascular carotid suture method. In the cortex at 1 and 3 days following MCA occlusions, HSP70 immunoreactive neurons were located outside areas of infarction and showed little evidence of DNA fragmentation. HSP70-stained cortical neurons were intermingled with TUNEL cells near the infarct, but extended for greater distances away from the infarct.

Focal hyperexpression of hemeoxygenase-1 protein and messenger RNA in rat brain caused by cellular stress following subarachnoid injections of lysed blood.

Induction of the hemeoxygenase-1 (ho-1) stress gene is of importance for rapid heme metabolism and protection against oxidative injury in vitro and in vivo. Although ho-1 expression is observed in glia following exposure to whole blood and oxyhemoglobin, expression is mild, and other stress genes are not induced simultaneously in this setting. Hemeoxygenase-1 can be induced by several other physiological stresses in addition to heme.

Expression of hsp70 mRNA is induced in the brain of transgenic mice overexpressing human CuZn-superoxide dismutase following transient global cerebral ischemia.

We examined hsp70 mRNA expression in the brains of transgenic (Tg) mice overexpressing CuZn-superoxide dismutase and in wild-type (Wt) littermates after 3 min of bilateral common carotid artery occlusion. Significant induction of hsp70 mRNA occurred in the hippocampus, the cortex, and other brain regions of the Tg mice 4 h after ischemia compared to the Wt mice. However, there was no histological damage in the brains of Tg and Wt mice as assessed by both Cresyl violet staining and by TUNEL staining for DNA fragmentation.

Induction of heme oxygenase-1 (HO-1) in glia after traumatic brain injury.

In this study we examined the induction of heme oxygenase-1 (HO-1) in glia in the traumatized rat brain. HO-1 was immunolocalized in fixed sections of brain 3 h to 5 days after injury. Induction of this enzyme in astrocytes, microglia/macrophages, and oligodendrocytes was evaluated using immunofluorescent double labeling with monoclonal antibodies to glial fibrillary acidic protein, complement C3bi receptor, and myelin basic protein.

Eliprodil prevents expression of the 70 kDa heat shock protein in MK801-injured neurones.

The present study examined whether eliprodil (SL 82.0715), an N-methyl-D-aspartate (NMDA) receptor antagonist acting on the polyamine sites induced expression of the 70 kDa heat shock protein (HSP70) in the rat brain. Whereas the NMDA channel blocker MK801 consistently induced HSP70 in posterior cingulate and retrosplenial cortices, eliprodil had no such effects even at the highest dose (50 mg/kg, intraperitoneally), supporting the idea that injury to the cerebrocortical neurones by NMDA receptor antagonists is probably related to specific sites of the receptor.

Global ischemia induces immediate-early genes encoding zinc finger transcription factors.

Ischemia induces immediate-early genes (IEGs) in brain. Since prolonged expression of some IEGs may precede neuronal death, some researchers have suggested that these IEGs mediate neuronal death. We therefore examined the effect of 5 and 10 min of global ischemia on the expression of the IEGs NGFI-A, NGFI-B, NGFI-C, egr-2, egr-3, and Nurr1 in gerbil brain.

Effects of phencyclidine on immediate early gene expression in the brain.

The N-methyl-D-aspartate receptor antagonist phencyclidine (PCP) is a psychotomimetic drug which produces schizophrenia-like psychosis. In animal studies it is toxic to neurons in the posterior cingulate and retrosplenial cortex and to cerebellar Purkinje cells. To find clues about the mechanism and pathways of PCP action, we studied the effect of systemic PCP administration (10 and 50 mg/kg, intraperitoneal) on the expression of immediate-early genes (IEGs) (c-fos, c-jun, egr-2, egr-3, NGFI-A, NGFI-B, NGFI-C, and Nurr1) using in situ hybridization histochemistry.

Induction of HSP70 in rat brain following subarachnoid hemorrhage produced by endovascular perforation.

Current experimental research on subarachnoid hemorrhage (SAH) has been limited by the lack of a small-animal model that physiologically resembles SAH and consistently demonstrates acute and delayed cellular injury. Recently, a model for inducing SAH by endovascular perforation of the internal carotid artery has been developed in the rat. This model physiologically resembles SAH.

Astrocyte survival and HSP70 heat shock protein induction following heat shock and acidosis.

Although severe acidosis is an important mediator of brain infarction, recent evidence suggests that mild acidosis may protect ischemic cells. The HSP70 heat shock protein is induced by acidosis in cultured cells and in ischemic brain and protects cells against many types of injury. Therefore, this study determined whether induction of heat shock proteins protects cultured astrocytes against acidosis.

MK-801 reduces uptake and stimulates efflux of excitatory amino acids via membrane depolarization.

MK-801 and related compounds reduce excitotoxic neuronal injury by blocking N-methyl-D-aspartate (NMDA) receptorgated ion channels. These agents also cause neuronal vacuolization and block glutamate-induced astrocyte swelling, effects that may be unrelated to actions at the NMDA receptor. In the present study, high concentrations of MK-801 (100-1,000 microM) caused uncompetitive inhibition of glutamate uptake in astrocyte and neuronal cultures and stimulated D-aspartate efflux from astrocytes.

Purkinje cell vulnerability to mild traumatic brain injury.

In this study we examined the cerebellar response to mild traumatic brain injury by assessing microglial activation and Purkinje cell loss. Activated microglia were identified using the antibodies OX-42 and ED-1 as well as isolectin B4. The anti-Purkinje cell antibody PEP-19 was used to evaluate Purkinje cell loss after injury.

Patient selection and treatment modalities for chronic anal fissure.

Background: Incontinence of feces or flatus is a serious complication of lateral internal sphincterotomy with a incidence of 0-35%. Multiple cofactors may predispose to fecal incontinence.

Methods: Review of 27 reported series of internal sphincterotomy and analysis of 34 consecutive cases of fecal incontinence seen by the author were carried out.

Heme oxygenase-1 (HO-1) protein induction in rat brain following focal ischemia.

The induction of the heme oxygenase-1 (HO-1) protein, also called HSP32, was compared to HSP70 heat shock protein induction following focal ischemia. Adult Sprague-Dawley male rats (n = 14) were subjected to either 30 min or 2 h of focal cerebral ischemia using the suture, middle-cerebral-artery (MCA) occlusion model. Controls (n = 4) had sham surgery.

Heme-oxygenase-1 induction in glia throughout rat brain following experimental subarachnoid hemorrhage.

The heme released following subarachnoid hemorrhage is metabolized by heme-oxygenase (HO) to biliverdin and carbon monoxide (CO) with the release of iron. The HO reaction is important since heme may contribute to vasospasm and increase oxidative stress in cells. HO is comprised of at least two isozymes, HO-2 and HO-1.

Subarachnoid injections of lysed blood induce the hsp70 stress gene and produce DNA fragmentation in focal areas of the rat brain.

Background And Purpose: Most experimental studies of subarachnoid hemorrhage have demonstrated little histological evidence of injury. In the present study we examined both the expression of the hsp70 heat-shock gene, a molecular marker of reversible neuronal injury, and DNA fragmentation, a marker of irreversible cell injury and death.

Methods: Lysed blood, whole blood, oxyhemoglobin, bovine serum albumin, and saline were injected into the cisterna magna of adult rats.