Abstract Details

Title Regulation of Angiogenic Factors in the Mouse Intrahippocampal Kainic Acid Model of Epileptogenesis

Topic Epilepsy

Presentation(s) IN9 - (-)

Poster/Presentation
Number 004

Objective

Background In this study, we used the mouse intrahippocampal kainic acid model to investigate the time course and cell-type specificity of angiogenic factor regulation and glial-vascular alterations during epileptogenesis in wild-type mice and mice lacking the glial water channel aquaporin-4 (AQP4).

Design/Methods 20 male CD1/C57B6 6-8 week old mice were were anesthetized and placed in a stereotactic frame where either 100 nL of kainic acid (4.35 mg/mL) or saline for controls was injected into the right dorsal hippocampus. Following kainic acid treatment, mice were behaviorally monitored for acute status epilepticus (SE) using the Racine scale. Mice were then sacrificed at 1, 4, 7 and 14 days post SE and processed for immunohistochemistry. Immunohistochemistry was performed for vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1), zona occludens 1 (ZO-1), glial fibrillary acidic protein(GFAP), aquaporin 4 (AQP4) and type IV collagen.

Results While no significant changes were observed in the contralateral hippocampus, the ipsilateral Stratum Lacunosum Moleculare (SLM) displayed an increase in vascular density beginning at 7 days post SE. No marked differences were observed between WT and AQP4-/- mice. WT mice displayed a reduction in VEGF immunoreactivity 14 days after the induction of spontaneous seizures(comparable to baseline levels), whereas astrocytes of AQP4-/-mice continued to up-regulate VEGF.

Conclusions The increased vascular density observed in the ipsilateral hippocampus may be due to a continual upregulation in angiogenic factors following kainic acid infusion. An up-regulation of VEGF and Ang-1 accompanied no significant changes in blood vessel morphology within the contralateral hippocampus, indicating that these factors may be playing extra-vascular roles. The continued up-regulation of this factor in AQP4-/- mice suggests that water homeostasis may play an integral role in vascular formation.

Authors/Disclosures
Kiran F. Rajneesh, MD, FAAN PRESENTER	An immediate family member of Dr. Rajneesh has stock in Crossliner.
	No disclosure on file
Devin K. Binder	No disclosure on file
Joseph F. Quinn, MD, FAAN (OHSU Neurology)	Dr. Quinn has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Retrophin. Dr. Quinn has received personal compensation in the range of $500-$4,999 for serving as a DSMB with Alzheimer's Disease Cooperative Study. Dr. Quinn has received personal compensation in the range of $500-$4,999 for serving as a DSMB with Alzheimer's Therapeutic Research Institute. Dr. Quinn has a non-compensated relationship as a consultant with Cognition Therapeutics that is relevant to AAN interests or activities.

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