Transient focal ischemia results in persistent and widespread neuroinflammation and loss of glutamate NMDA receptors.
Stroke is accompanied by neuroinflammation in humans and animal models. To examine the temporal and anatomical profile of neuroinflammation and NMDA receptors (NMDAR) in a stroke model, rats (N=17) were subjected to a 90 min occlusion of the middle cerebral artery (MCAO) and compared to sham (N=5) and intact (N=4) controls. Striatal and parietal cortical infarction was confirmed by MRI 24h after reperfusion. Animals were killed 14 or 30-40 days later and consecutive coronal cryostat sections were processed for quantitative autoradiography with the neuroinflammation marker [(3)H]PK11195 and the NMDAR antagonist [(3)H]MK801. Significantly increased specific binding of [(3)H]PK11195 relative to non-ischemic controls was observed in the ipsilateral striatum (>3 fold, p<0.0001), substantia innominata (>2 fold) with smaller (20%-80%) but statistically significant (p=0.002-0.04) ipsilateral increases in other regions partially involved in the infarct such as the parietal and piriform cortex, and in the lateral septum, which was not involved in the infarct. Trends for increases in PBR density were also observed in the contralateral hemisphere. In the same animals, NMDAR specific binding was significantly decreased bilaterally in the septum, substantia innominata and ventral pallidum. Significant decreases were also seen in the ipsilateral striatum, accumbens, frontal and parietal cortex. The different anatomical distribution of the two phenomena suggests that neuroinflammation does not cause the observed reduction in NMDAR, though loss of NMDAR may be locally augmented in ipsilateral regions with intense neuroinflammation. Persistent, bilateral loss of NMDAR, probably reflecting receptor down regulation and internalization, may be responsible for some of the effects of stroke on cognitive function which cannot be explained by infarction alone.
Dhawan
Jasbeer
J
Medical Department, Brookhaven National Laboratory, Building 490, Upton, NY 11973, USA.
Benveniste
Helene
H
Nawrocky
Marta
M
Smith
S David
SD
Biegon
Anat
A
D000818:Animals; D001345:Autoradiography; D004660:Encephalitis / Q000209:etiology / Q000276:immunology / Q000473:pathology*; D005260:Female; D007091:Image Processing, Computer-Assisted; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000276:immunology / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000209:etiology / Q000276:immunology / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*
D016194:Receptors, N-Methyl-D-Aspartate