We investigated levels and compositions of N-acylethanolamines (NAEs) and their precursors, N-acyl phosphatidylethanolamines (N-acyl PEs), in a rat stroke model applying striatal microdialysis for glutamate assay. Rats (n ¼ 18) were treated with either intravenous saline (control), NMDA receptor antagonist MK801 (1 mg/kg), or CB1 receptor antagonist SR141716A (1 mg/kg) 30 min after permanent middle cerebral artery occlusion (MCAO). MK801 significantly attenuated the release of glutamate in the infarcted striatum (79 ± 22 lmol/L) as compared with controls (322 ± 104 lmol/L). The administration of CB1 antagonist SR141716A had no statistically significant effect on glutamate release (340 ± 89 lmol/L), but reduced infarct volume at 5 h after MCAO significantly by approximately 40%, whereas MK801 treatment resulted in a non-significant (18%) reduction of infarct volume. In controls, striatal and cortical NAE concentrations were about 30-fold higher in the infarcted than in the non-infarcted hemisphere, whereas ipsilateral N-acyl phosphatidylethanolamine (N-acyl PE) levels exceeded contralateral levels by only a factor of two to three. Treatment with MK801 or SR141716A, or glutamate release in the infarcted tissue, had no significant effect on these levels. NAE accumulation during acute stroke may be due to increased synthesis as well as decreased degradation, possibly by inhibition of fatty acid amide hydrolase (FAAH).

No abstract

Background and Purpose-Both application of neurotrophic factors like brain-derived neurotrophic factor (BDNF) and constraint-induced movement therapy like forced arm use have been shown to potentially improve outcome after stroke. The aim of the present study was to check whether postischemic long-term outcome correlates to specific modifications in the abundance of various neurotransmitter receptors. Methods-Adult male Wistar rats were subjected to photothrombotic ischemia and assigned to various treatment groups (nϭ5 each) with end points at 3 and 6 weeks: (1) ischemic control (saline); (2) BDNF (ischemia, 20 g BDNF); (3) forced arm use (ischemia, saline, and ipsilateral plaster cast for 5 or 14 days for the 3-and 6-week groups, respectively); and (4)

Background-Hyperbaric oxygenation (HBO) after focal cerebral ischemia reduces infarct size and improves outcome when applied early after stroke. Here, we evaluated effects of HBO on permanent focal cerebral ischemia and applied magnetic resonance imaging (MRI) monitoring to study lesion evolution. Methods-Rats underwent permanent middle cerebral artery occlusion (MCAO). Two hours later, animals were treated with HBO (100% O 2 /2 atm; nϭ17) for 1 hour or treated with room air (nϭ17). Animals underwent serial MRI studies (DWI, PI, T2) beginning 90 minutes after MCAO. Neuroscore was assessed (5-point rating scale). Animals were euthanized and brains were 2,3,5-triphenyltetrazolium chloride (TTC)-stained for infarct volume calculation 120 hours after MCAO. Immunohistochemistry was performed with antibodies against c-FOS and 4-hydroxy-2-nonenal-modified proteins (HNE) to check for effects of oxidative stress caused by HBO treatment. Results-HBO reduced infarct volume by 38% (PϽ0.001). As shown by MRI, neuroprotection began 5 hours after ischemia and remained effective for 5 days. The relative regional cerebral blood flow was not different between groups at 3.5 and 5 hours after occlusion. There was less neurological deficit in HBO-treated animals compared with controls (PϽ0.05). Lipid peroxidation of cerebral vessels after HBO treatment as measured by HNE staining and pattern of c-FOS induction were not significantly different between groups at 3.5 and 8 hours after ischemia. Conclusion-As monitored by MRI HBO treatment reversed ischemic lesion size between 3 and 5 hours after ischemia and achieved a long-lasting neuroprotective effect without significant oxidative damage.

Granulocyte-colony stimulating factor (G-CSF) is a hematopoietic growth factor that controls proliferation and differentiation of neural stem cells. Although recent studies have begun to explore G-CSF-related mechanisms of action in various disease models, little is known about its function in the healthy brain. In the present study, the effect of G-CSF deficiency on memory formation and motor skills was investigated. The impact of G-CSF deficiency on the structural integrity of the hippocampus was evaluated by analyzing the generation of doublecortin-expressing cells, the amount of bromodeoxyurine-labeled cells, the dendritic complexity in hippocampal neurons, the binding densities of NMDA and GABA A receptors and the induction of long-term potentiation (LTP). G-CSF deficiency caused a disruption in memory formation and in the development of motor skills. These impairments were associated with reduced ligand binding densities of NMDA receptors in hippocampal subfields CA3 and the dentate gyrus. The reduced excitation was potentiated by increased ligand binding densities of GABA A receptors resulting in a relative shift in favor of inhibition and impaired behavioral performance. These alterations were accompanied by impaired induction of LTP in the CA1 region. Moreover, G-CSF deficiency led to decreased dendritic complexity in hippocampal neurons in the dentate gyrus and the CA1 region. G-CSF deficiency also caused a reduction of neuronal precursor cells in the dentate gyrus. These findings confirm G-CSF as an essential neurotrophic factor, and point to a role in the proliferation, differentiation and functional integration of neural cells necessary for the structural and functional integrity of the hippocampal formation.

Background and Purpose-Some patients develop severe brain edema after complete middle cerebral artery occlusion, whereas others do not. Aquaporin-4 (AQP4) is the main water channel in the brain and has been shown to be critical for the development of brain edema after ischemia. We asked whether genetic variation in the AQP4 gene is related to the severity of brain edema after middle cerebral artery occlusion. Methods-We genotyped 10 single nucleotide polymorphisms distributed across the AQP4 gene in 41 patients with middle cerebral artery occlusion with and without severe brain edema and assessed single marker association as well as the linkage dysequilibrium structure across AQP4. Results-One single nucleotide polymorphism (rs9951307) at the 3Ј end of AQP4 was associated with severe brain edema (dominant model, Pϭ0.01; OR, 0.10; 95% CI, 0.02 to 0.49 for the protective G-allele). Linkage dysequilibrium across AQP4 was low; no clear haplotype blocks could be identified for the assessment of haplotype association. Conclusions-This explorative study shows that genetic variation in AQP4 might contribute to brain edema formation after middle cerebral artery occlusion and warrants further investigation.

No abstract

No abstract