Neuroscience letters
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Blocking the development of epilepsy (epileptogenesis) is a fundamental research area with the potential to provide large benefits to patients by avoiding the medical and social consequences that occur with epilepsy and lifelong therapy. Human clinical trials attempting to prevent epilepsy (antiepileptogenesis) have been few and universally unsuccessful to date. In this article, we review data about possible pathophysiological mechanisms underlying epileptogenesis, discuss potential interventions, and summarize prior antiepileptogenesis trials. Elements of ideal trials designs for successful antiepileptogenic intervention are suggested.
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Neuroscience letters · Jun 2011
ReviewThe time course of acquired epilepsy: implications for therapeutic intervention to suppress epileptogenesis.
Relatively little is known about the time course of the development of spontaneous recurrent seizures (i.e., epileptogenesis) after brain injury in human patients, or even in animal models. This time course is determined, at least in part, by the underlying molecular and cellular mechanisms responsible for acquired epilepsy. An understanding of the critical mechanistic features of acquired epilepsy will be useful, if not essential, for developing strategies to block or suppress epileptogenesis. ⋯ Although the classical view of the development of epileptogenesis is a step-function of time after the brain injury, with a latent period present between the brain injury and the first unprovoked seizure, the data described here show that seizure frequency was a sigmoid function of time after the insult in both animal models. Furthermore, the spontaneous recurrent seizures often occurred in clusters, even shortly after the first spontaneous seizure. These data suggest that (1) epileptogenesis is a continuous process that extends past the first spontaneous clinical seizure, (2) seizure clusters can obscure this continuous process, and (3) the potential time for administration of a therapy to suppress acquired epilepsy extends well past the first clinical seizure.
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Neuroscience letters · Jun 2011
ReviewAnti-epileptogenesis in rodent post-traumatic epilepsy models.
Post-traumatic epilepsy (PTE) accounts for 10-20% of symptomatic epilepsies. The urgency to understand the process of post-traumatic epileptogenesis and search for antiepileptogenic treatments is emphasized by a recent increase in traumatic brain injury (TBI) related to military combat or accidents in the aging population. ⋯ Also, current understanding of the mechanisms and biomarkers for PTE as well as factors associated with preclinical study designs are discussed. Finally, we summarize the attempts to prevent PTE in experimental models.
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Neuroscience letters · Jun 2011
Clonidine as adjuvant for oxybuprocaine, bupivacaine or dextrorphan has a significant peripheral action in intensifying and prolonging analgesia in response to local dorsal cutaneous noxious pinprick in rats.
The aim of the study was to evaluate co-administration of clonidine with oxybuprocaine (ester type), bupivacaine (amide type) or dextrorphan (non-ester or non-amide type) and to see whether it could have a peripheral action in enhancing local anesthesia on infiltrative cutaneous analgesia in rats. Cutaneous analgesia was evaluated by a block of the cutaneous trunci muscle reflex (CTMR) in response to local dorsal cutaneous noxious pinprick in rats. The analgesic effect of the addition of clonidine with oxybuprocaine, bupivacaine or dextrorphan by subcutaneous injection was evaluated. ⋯ Oxybuprocaine showed more potent cutaneous analgesia than bupivacaine or dextrorphan in rats. Co-administration of oxybuprocaine, bupivacaine or dextrorphan with clonidine increased the potency and duration on infiltrative cutaneous analgesia. The addition of clonidine to bupivacaine (amide type) elicits more effective cutaneous analgesia than oxybuprocaine (ester type) or dextrorphan (non-ester or non-amide type).
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Neuroscience letters · Jun 2011
Oral fish oil restores striatal dopamine release after traumatic brain injury.
Omega-3 fatty acid administration can affect the release of neurotransmitters and reduce inflammation and oxidative stress, but its use in traumatic brain injury (TBI) has not been described extensively. We investigated the effect of 7 day oral fish oil treatment in the recovery of potassium evoked dopamine release after TBI. ⋯ There was no effect of fish oil treatment on extracellular levels of dopamine metabolites such as 3,4-dihydroxyphenylacetic acid and homovanillic acid. These results suggest the therapeutic potential of omega-3 fatty acids in restoring dopamine neurotransmission deficits after TBI.