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Intraischemic moderate hypothermia generally protects the brain against ischemic cell death, while hypothermia instigated several hours into the reperfusion phase is considered to be less effective. Here we report the effect of hypothermia (32.5°-33.5°C) of 5-h duration, initiated at 2, 6, 12, 24 and 36 h into the recirculation phase following 10 min of transient cerebral ischemia, on ischemic neu
Abstract— Growth factors stimulate cellular protein synthesis, but the intracellular signaling mechanisms that regulate initiation of mRNA translation in neurons have not been clarified. A rate‐limiting step in the initiation of protein synthesis is the formation of the ternary complex among GTP, eukaryotic initiation factor 2 (elF‐2), and the initiator tRNA. Here we report that genistein, a speci
Following stress such as heat shock or transient cerebral ischemia, global brain protein synthesis initiation is depressed through modulation of eucaryotic initiation factor (eIF) activities, and modification of ribosomal subunits. Concomitantly, expression of a certain class of mRNA, heat-shock protein (HSP) mRNA, is induced. Here we report that the activity of eucaryotic initiation factor-2 (eIF
Abstract: The changes in the levels of tyrosine‐phosphorylated proteins in the cytosolic fraction of the rat hippocampus subjected to severe hypoglycemia were analyzed. A marked increase in tyrosine phosphorylation of a 43‐kDa protein was observed at 30 min of isoelectric EEG and 30 min and 1 h of recovery. Immunostaining of the same blot with antibody against mitogen‐activated protein (MAP) kinas
Neuronal protein synthesis is severely depressed following stress such as heat-shock, hypoxia, and hypoglycemia. Following reversible cerebral ischemia, protein synthesis is transiently inhibited in ischemia-resistant areas, but persistently depressed in vulnerable brain regions. Eukaryotic initiation factor 2 (elF-2) activity, that is, the formation of the ternary complex elF-2 · GTP · initiator
The response of excitatory amino acid transporter binding sites in the rat brain to 10 min of cerebral ischemia induced by bilateral common carotid occlusion combined with hypotension was examined. We observed a transient increase in the density of transporter binding sites that was first noticeable at 5 min post-recovery and persisted for 48 h. The increase in binding sites was found throughout t
Abstract: The time course for the ischemia‐induced changes in the subcellular distribution of protein kinase C (PKC) (α), (β311). and (γ) and the activity of PKC were studied in the neocortex of rats subjected to 1, 2, 3, 5, 10, and 15 min of global cerebral ischemia. In the particulate fraction, a 14‐fold increase in PKC (γ) levels was seen at 3 min of ischemia, which further increased at 5–15 m
Growth factor receptors activate protein tyrosine kinases, which are important for cell growth and survival. The protein tyrosine kinase (PTK) activity and the levels of phosphotyrosine (Ptyr) containing proteins were studied in the rat neocortex exposed to 15 min of transient cerebral ischaemia. The levels of the Ptyr containing proteins increase during recovery in the synaptosomal fraction, whil
Binding of 125I-insulin-like growth factor-1 (125I-IGF-1) to rat brain slices was studied after 15 min of two-vessel occlusion ischemia and 1 h to 4 days of recirculation. Ligand binding in the hippocampus increased at 6 h post ischemia in the CA1 and CA3 regions and the dentate gyrus, suggesting that the IGF-1 receptors were up-regulated, while no change was seen in neocortex and striatum. Intrac
Excitatory amino acids are implicated in the development of neuronal cell damage following periods of reversible cerebral ischemia or insulin-induced hypoglycemic coma. To explore the importance of glutamate receptor activation in the posthypoglycemic phase, we exposed rats to 20 min of insulin-induced severe hypoglycemia. The rats were treated immediately after the hypoglycemic insult with four r
The effect of different glutamate‐receptor antagonists on the induction of cortical spreading depression of Leao and of cortical anoxic membrane depolarization were investigated in the anaesthetized rat. Spreading depression (SD), elicited by mechanical stimulation of the cortical surface, was inhibited by the non‐competitive N‐methyl‐d‐aspartate (NMDA)‐receptor blocker, (±)‐5‐methyl‐10,11‐dihydro
The brain noradrenaline (NA) system is known to modulate ischemic neuronal damage, and the turnover of NA has been suggested to increase in the early recovery period following cerebral ischemia. Using HPLC and gas chromatography-mass spectrometry we analyzed the tissue levels of NA and its metabolites, 3,4-dihydroxyphenylethyleneglycol (DHPG) and 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG), in
The ultrastructural changes in the pyramidal neurons of the CA1 region of the hippocampus were studied 6 h, 24 h, 48 h, and 72 h following a transient 10 min period of cerebral ischemia induced by common carotid occlusion combined with hypotension. The pyramidal neurons showed delayed neuronal death (DND), i.e. at 24 h and 48 h postischemia few structural alterations were noted in the light micros
Glutamatergic transmission is an important factor in the development of neuronal death following transient cerebral ischemia. In this investigation the effects of N-methyl-D-aspartate (NMDA) and non-NMDA receptor antagonists on neuronal damage were studied in rats exposed to 10 min of transient cerebral ischemia induced by bilateral common carotid occlusion combined with hypotension. The animals w
Changes in ligand binding to adrenoceptors ([3H]prazosin to α1-receptors, [3H]idazoxan to α2-receptors and [125I]cyanopindolol to β-receptors) following transient cerebral ischemia were investigated using autoradiographic methods. The binding was quantified in brain sections from control rats, rats subjected to 15 min of 2-vessel occlusion ischemia, and rats with recirculation times of 1 h, 1 week
Abstract: The changes in the levels of protein kinase C [PKC(α, βII, γ)] were studied in cytosolic and particulate fractions of striatal homogenates from rats subjected to 15 min of cerebral ischemia induced by bilateral occlusion of the common carotid arteries and following 1 h, 6 h, and 48 h of reperfusion. During ischemia the levels of PKC(βII) and ‐(γ) increased in the particulate fraction to
: The effect of hypothermia on the ischemia‐induced changes in the subcellular distribution of protein kinase C (PKC)(γ), ‐(βII), and ‐(α) and the activity of PKC was studied in striatal homogenates of rats subjected to 20 min of cerebral ischemia. The effect of post‐ischemic cooling was also studied. During normothermic ischemia, PKC(γ) and ‐(βII) increased 3.9‐and 2.9‐fold, respectively, in the
Glutamate is an important factor in the mechanisms of neuronal damage following cerebral ischemia. Blockade of one type of glutamate receptor, the N-methyl-D-aspartate (NMDA) receptor, decreases brain infarct size in experimental models of permanent focal ischemia, but protection in models of transient reversible ischemia is ambiguous. We investigated the effect of the noncompetitive NMDA receptor
