Apolipoprotein E4 impairs spontaneous blood brain barrier repair following traumatic brain injury.
MouseTBIControlled cortical impactWildtype C57Bl/6 (Jackson Laboratories) and humanised APOE3 or APOE4 targeted replacement mice on a C57BL/6J backgroundMalen = n = 3 per group for the longitudinal gadolinium MRI cohort;…Intraperitoneal20 mg/kg in 10 mL/kg for the initial dose, then repeat dose…First dose 15 min post-injury
Model: Controlled cortical impact, 4 mm craniotomy over the left parietal bone, impact at 5.25 m/s velocity with 1.5 mm tissue deformation; sham animals received anaesthesia and incision without impact
Blood brain barrier permeability peaked at day 1 (411% increase in ipsilateral cortex Evans blue) and closed spontaneously by 7 to 10 days. Cyclosporin A attenuated microvessel MMP-9 responses and returned barrier permeability to sham levels by 5 days post-injury, whereas vehicle mice remained 135%…
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