Old age is associated with an enhanced susceptibility to stroke and poor recovery from brain injury, but the cellular processes underlying these phenomena are not well understood. Potential mechanism underlying functional recovery after brain ischemia in aged subjects include neuroinflammation, changes in brain plasticity-promoting factors, unregulated expression of neurotoxic factors, or differen

This unit describes two methods of in situ hybridization: one uses an 35S-labeled oligonucleotide probe and the other uses a digoxigenin-labeled oligonucleotide probe on frozen, cryostat-sectioned samples. These methods allow detection of the physical distribution and expression levels of target mRNA. Protocols are also included for labeling the probes and preparing the sample material.

Seizure activity regulates gene expression for glial cell line-derived neurotrophic factor (GDNF) and neurturin (NRTN), and their receptor components, the transmembrane c-Ret tyrosine kinase and the glycosylphosphatidylinositol-anchored GDNF family receptor (GFR) α1 and α2 in limbic structures. We demonstrate here that epileptogenesis, as assessed in the hippocampal kindling model, is markedly sup

Loss of function mutations in the gene encoding the cysteine protease inhibitor, cystatin B (CSTB), are responsible for the primary defect in human progressive myoclonus epilepsy (EPM1). CSTB inhibits the cathepsins B, H, L and S by tight reversible binding, but little is known regarding its localization and physiological function in the brain and the relation between the depletion of the CSTB pro

The levels of brain-derived neurotrophic factor (BDNF) vary between different forebrain areas and show region-specific changes after cerebral ischemia. The present study explores the possibility that the levels of endogenous BDNF determine the susceptibility to ischemic neuronal death. To block BDNF activity the authors used the TrkB-Fc fusion protein, which was infused intraventriculary in rats d

Expression of mRNAs for neuropeptide Y (NPY) and its receptor subtypes Y1 (Y1-R), Y2 (Y2-R) and Y5 (Y5-R) was studied in adult rat brain using in situ hybridization after 40 rapidly recurring seizures induced with 5-min interval by hippocampal kindling stimulations. At 2-4 h post-seizure, NPY mRNA levels were markedly elevated in dentate granule cells, CA1 and CA3 pyramidal layers, amygdala and pi

Neural stem cell lines represent a homogeneous source of cells for genetic, developmental, and gene transfer and repair studies in the nervous system. Since both gene transfer of neurotrophic factors and cell replacement strategies are of immediate interest for therapeutical purposes, we have generated BDNF-secreting neural stem cell lines and investigated to what extent different endogenous level

Cellular localization and tissue levels of BDNF protein were studied using immunocytochemistry and enzyme immunoassay, respectively, in the cortex and striatum at different reperfusion times (0-24 h) after 2 h of unilateral middle cerebral artery occlusion (MCAO) in rats. The distribution of neuronal injury was analyzed in NeuN-, cresyl violet-, and Fluoro-Jade-stained sections. At 2 h postischemi

Cajal-Retzius (CR) cells of the cerebral cortex express receptors for the neurotrophin brain-derived neurotrophic factor (BDNF) and downregulate expression of the extracellular matrix protein Reelin during early postnatal development, coincident with the onset of cortical BDNF expression. During this period, mice lacking BDNF have elevated levels of Reelin in CR cells. Acute BDNF stimulation of co

Expression of p75 neurotrophin receptor and survival of medium-sized spiny projection neurons and cholinergic interneurons in the rat striatum were studied using immunocytochemistry at different times after transient, unilateral middle cerebral artery occlusion. Thirty minutes of middle cerebral artery occlusion caused a major loss of projection neurons, identified by their immunoreactivity to dop

Preischemic hyperglycemia or superimposed hypercapnia exaggerates brain damage caused by transient forebrain ischemia. Because high regional levels of brain-derived neurotrophic factor (BDNF) protein correlate with resistance to ischemic damage, we studied the expression of BDNF mRNA using in sire hybridization in rats subjected to 10 minutes of forebrain ischemia under normoglycemic, hyperglycemi

The suspension of embryonic locus coeruleus (LC) was transplanted into outbred albino rat hippocampus after its preliminary 6-hydroxy-dopamine-induced denervation. Immunohistochemical and morphometric analysis revealed that 3 months after the transplantation, embryonic noradrenergic LC cells which have completed their histogenesis in recipient hippocampus, appear as differentiated multipolar and f

Brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and platelet-derived growth factor (PDGF) exert trophic effects on striatal neurons in vitro, which raises the possibility that these growth factors might also counteract neuronal death provoked by various insults. We have found that BDNF and NT-3, but neither PDGF-AA nor -BB, added 24 h before the insult ameliorated hypoglycemic neu

In situ hybridization was used to study expression of mRNAs for members of the nerve growth factor (NGF) family in the rat brain after 2 and 10 min of forebrain ischemia and 1 and 30 min of insulin-induced hypoglycemic coma. Two hours after the ischemic insults, the level of brain-derived neurotrophic factor (BDNF) mRNA was markedly increased in the granule cells of the dentate gyrus, and at 24 h

Kindling, induced by repeated subconvulsive electrical or chemical stimulations leads to progressive and permanent amplification of seizure activity, culminating in generalized seizures. We report that kindling induced by electrical stimulation in the ventral hippocampus leads to a marked and transient increase of mRNA for NGF and BDNF in the dentate gyrus, the parietal cortex, and the piriform co

Inversion of the early component of IPSPs in neurons of the sensorimotor cortex by artificial hyperpolarization of the membrane was demonstrated in cats immobilized by myorelaxants in acute experiments. The late component of IPSP was not inverted. Amplitudes of the early component of IPSPs were decreased by the membrane depolarization while the late component was completely reduced. The input resi

Inversion of the early component of IPSPs in pyramidal neurons of the sensorimotor cortex by intracellular injection of chloride ions was demonstrated in cats immobilized by myorelaxants in acute experiments under moderate composed anesthesia (40 mg/kg nembutal and 20 mg/kg chloralose intraperitoneally). The late component of IPSPs as well as the post-burst hyperpolarization in pyramidal neurons w

The aim of this study is to examine the reception of Origen of Alexandria (185-253/54) in the eschatological thought ofJerome of Stridon (347-419/20). Jerome, who was a Christian ascetic writer and a biblical commentator, relied heavily on Origen’s works during the first part of his career. Due to the Origenist controversy, which took place in the 390s and was initiated by Bishop Epiphanius of Sal