Anamnestic Recall of Stroke-Related Deficits

Abstract

Background and Purpose-Anamnestic recall of stroke-related deficits is a common clinical observation, especially during periods of systemic infection. The pathophysiology of this transient re-emergence of neurological dysfunction is unknown. Methods-Male Lewis rats underwent 3 hours middle cerebral artery occlusion and were treated with lipopolysaccharide or saline at the time of reperfusion. The delayed-type hypersensitivity (DTH) response to myelin basic protein was examined 28 days after middle cerebral artery occlusion. Changes in behavioral outcomes were assessed after DTH testing and repeat administration of lipopolysaccharide or saline at 34 days. At the time of euthanasia (36 days), the immunologic response of splenocytes to myelin basic protein, neuron-specific enolase, and proteolipid protein was determined by enzyme-linked immunospot assay and the number of lymphocytes in the brain determined by immunocytochemistry. Results-Animals treated with lipopolysaccharide at middle cerebral artery occlusion had a greater DTH response to myelin basic protein than animals treated with saline. Among those animals that had fully recovered on a given behavioral test before DTH testing, those treated with lipopolysaccharide at middle cerebral artery occlusion displayed more neurological deterioration after DTH testing and had more CD8 ϩ lymphocytes within the ischemic core of the brain. Furthermore, the Th1 immune response to brain antigens in the spleen was more robust among those animals that deteriorated after DTH testing and there were more CD4 ϩ lymphocytes in the penumbral region of animals with a Th1 response to myelin basic protein. Conclusions-Our

Neuronal Interleukin-4 as a Modulator of Microglial Pathways and Ischemic Brain Damage

“…Focal ischemia was induced by unilateral occlusion of the left middle cerebral artery (MCA) and the left common carotid artery (CCA) (MCA/CCAo), as we have described previously (Aronowski et al, 2000;Zhao et al, 2009b). Briefly, male C57BL/6 mice (10 -12 weeks old) or IL-4 -green fluorescent protein (GFP) reporter mice (C.129-Il4 tm1Lky /J; The Jackson Laboratory) were anesthetized with 0.35 g/kg chloral hydrate intraperitoneally.…”

“…The primary brain cells in culture were harvested and washed with PBS and then lysed in TRIzol reagent. RT-PCR analyses were done as described previously (Zhao et al, , 2009a. We used glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene as an internal standard.…”

“…The cortices of E18 prenatal embryos were dissected and dissociated by trituration as we described previously (Kim et al, 2004;Zhao et al, 2009b), with some modification. The dissociated cells were plated on poly-L-lysine-coated culture plates in Neurobasal medium with B27 at 300 -700 cells/mm 2 .…”

“…Nine-to 12-d-old primary cortical neurons in culture were subjected to oxygen-glucose deprivation (OGD) injury, as we reported previously (Zhao et al, 2009b). Briefly, the culture media were replaced with Neurobasal medium (Invitrogen) without glucose, and the cultures were placed in a gas-tight humidified chamber filled with 5% CO 2 /95% N 2 for 15 min, 30 min, 2 h, or 24 h. At the end of OGD, glucose at 4.5 mg/ml was added into the culture dish, and the cells were then returned to their original culture condition and incubated for 6 -24 h for reperfusion.…”

“…It has also been postulated that activation of the IL-4 receptor (IL-4R) by IL-4 itself leads to activation of the transcription factor peroxisome proliferator activated receptor ␥ (PPAR␥). Augmentation of PPAR␥ and its pathways-in part by modulating the function of microglia, the resident macrophages of the CNS-has been demonstrated to reduce brain injury after ischemic and hemorrhagic stroke (Luo et al, 2006;Tureyen et al, 2007;Zhao et al, , 2009b.…”