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The improved task performance of lesioned animals suggests a therapeutic effect of this manipulation, independent of BDNF. This effect is sensitive to the temporal administration of treatment.

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Therapeutic effects of PSD-95 inhibition have been demonstrated in numerous studies of stroke; however only few studies have assessed the effects of PSD-95 inhibitors in traumatic brain injury (TBI). As the pathophysiology of TBI partially overlaps with that of stroke, PSD-95 inhibition may also be an effective therapeutic strategy in TBI. The objectives of the present study were to assess the effects of a dimeric inhibitor of PSD-95, UCCB01-144, on excitotoxic cell death in vitro and outcome after experimental TBI in rats in vivo. In addition, the pharmacokinetic parameters of UCCB01-144 were investigated in order to assess uptake of the drug into the central nervous system of rats. After a controlled cortical impact rats were randomized to receive a single injection of either saline or two different doses of UCCB01-144 (10 or 20 mg/kg IV) immediately after injury. Spatial learning and memory were assessed in a water maze at 2 weeks post-trauma, and at 4 weeks lesion volumes were estimated. Overall, UCCB01-144 did not protect against NMDA-toxicity in neuronal cultures or experimental TBI in rats. Important factors that should be investigated further in future studies assessing the effects of PSD-95 inhibitors in TBI are discussed.

Voluntary exercise has previously been shown to enhance cognitive recovery after acquired brain injury (ABI). The present study evaluated effects of two differentially distributed protocols of delayed, voluntary exercise on cognitive recovery using an allocentric place learning task in an 8-arm radial maze. Fifty-four Wistar rats were subjected to either bilateral transection of the fimbria-fornix (FF) or to sham surgery. Twenty-one days postinjury, the animals started exercising in running wheels either for 14 consecutive days (FF/exercise daily [ExD], sham/ExD) or every other day for 14 days (FF/exercise every second day [ExS], sham/ExS). Additional groups were given no exercise treatment (FF/not exercise [NE], sham/NE). Regardless of how exercise was distributed, we found no cognitively enhancing effects of exercise in the brain injured animals. Design and protocol factors possibly affecting the efficacy of post-ABI exercise are discussed.