Magnetic resonance molecular imaging of post-stroke neuroinflammation with a P-selectin targeted iron oxide nanoparticle.

We have developed a magnetic resonance molecular imaging method using a novel iron-oxide contrast agent targeted towards P-selectin - MNP-PBP (magnetic nanoparticle-P-selectin binding peptide) - to image endothelial activation following cerebral ischemia/reperfusion. MNP-PBP consists of approximately 1000 PBP ligands (primary sequence: GSIQPRPQIHNDGDFEEIPEEYLQ GGSSLVSVLDLEPLDAAWL) conjugated to a 50 nm diameter aminated dextran iron oxide particle. In vitro P- and E-selectin binding was assessed by competition ELISA. Transient focal cerebral ischemia was induced in male C57/BL 6 mice followed by contrast injection (MNP-PBP; MNP-NH2; Feridex; MNP-PBP-FITC) at 24 h after reperfusion and T(2) magnetic resonance imaging at 9.4 T was performed. Infarction and microvasculature accumulation of contrast agent was assessed in coronal brain sections. MNP-PBP attenuated antibody binding to P-selectin by 34.8 +/- 1.7%. P-selectin was preferentially increased in the infarct hemisphere and MNP-PBP-FITC accumulation in the infarct hemisphere microvasculature was observed. Compared with the nontargeted iron oxide agents MNP-NH2 and Feridex, MNP-PBP showed a significantly greater T(2) effect within the infarction. MR imaging of P-selectin expression with a targeted iron oxide nanoparticle contrast agent may reveal early endothelial activation in stroke and other neuroinflammatory states.

Development of a model of recurrent stroke consisting of a mild transient stroke followed by a second moderate stroke in rats.

Recurrent stroke often consists of a transient ischemic attack or mild stroke followed by a moderate stroke. Lacking is knowledge of the mechanisms of interaction of such multiple ischemic insults. Our aim was to develop a rat model of recurrent stroke and to test whether such multiple insults would enhance brain injury. A mild focal ischemic insult was produced by transient (40min) occlusion of the middle cerebral artery (MCAO) and this resulted in scattered necrosis and areas of increased labeling of astrocytes with glial fibrillary acidic protein. Additional animals were subjected to a moderate stroke alone or a recurrent stroke-a mild stroke followed 3 days later by a moderate stroke (60min MCAO). Damage was dependent on the proximal or distal cerebral cortical location from the occlusion (P<0.007) and the type of stroke insult (mild, moderate or recurrent, P<0.002). Following recurrent stroke, the cumulative injury score was similar to a mild stroke in distal parietal cortex but enhanced proximally. Recurrent stroke also resulted in changes in magnetic resonance imaging T(2), in neuronal microtubule associated protein2, in reactive astrocytes and in microglia/macrophages that were enhanced in proximal but not distal parietal cortex. This model demonstrates that when a minor stroke is combined with a second stroke, both distributed within the same middle cerebral artery territory, there are different injury processes regionally. Proximally, damage exceeds that of the first insult whereas distally the response is consistent with a tolerance to the second insult.

Limbic encephalitis - a review.

The clinical features of limbic encephalitis are diverse and early diagnosis of the disorder is frequently difficult. Four patients with limbic encephalitis are described. An antineuronal antibody was identified in three of these patients. Antibodies directed against voltage-gated potassium channels, the N-methyl-D-aspartate receptor and an unidentified neuropil antigen were each found in one patient. The fourth patient had multifocal paraneoplastic encephalitis associated with small cell lung cancer. The clinical and imaging findings associated with these antibodies and the other antineuronal antibodies described in patients with limbic encephalitis are reviewed. An approach to the diagnosis and management of limbic encephalitis is presented.

Superior sagittal sinus obstruction and tuberculous abscess.

Intracranial tumours such as meningiomas may occasionally produce raised intracranial pressure by occluding a venous sinus. More uncommonly, midline tumours in the occipital regions of the skull can produce elevated intracranial pressure by non-thrombotic compression of the superior sagittal sinus. We present a case of raised intracranial pressure secondary to non-thrombotic obstruction of the superior sagittal sinus by a midline tuberculous abscess.