Experimental neurology
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Experimental neurology · Jun 2008
Comparative StudyMild traumatic brain injury to the infant mouse causes robust white matter axonal degeneration which precedes apoptotic death of cortical and thalamic neurons.
The immature brain in the first several years of childhood is very vulnerable to trauma. Traumatic brain injury (TBI) during this critical period often leads to neuropathological and cognitive impairment. Previous experimental studies in rodent models of infant TBI were mostly concentrated on neuronal degeneration, while axonal injury and its relationship to cell death have attracted much less attention. ⋯ At early stages post-injury no evidence of excitotoxic neuronal death at the impact site was found. At 48 h apoptotic cell death was reduced and paralleled with the reduction in the number of APP-labeled axonal profiles. Our data suggest that early degenerative response to injury in axons of the cingulum and external capsule may cause disconnection between cortical and thalamic neurons, and lead to their delayed apoptotic death.
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Experimental neurology · Jun 2008
Comparative StudyAxotomy or compression is required for axonal sprouting following end-to-side neurorrhaphy.
End-to-side (ETS) nerve repair remains an area of intense scrutiny for peripheral nerve surgeon-scientists. In this technique, the transected end of an injured nerve, representing the "recipient" is sutured to the side of an uninjured "donor" nerve. Some works suggest that the recipient limb is repopulated with regenerating collateral axonal sprouts from the donor nerve that go on to form functional synapses. ⋯ Progressively more injurious models were associated with improved recipient nerve reinnervation (epineurotomy: 184+/-57.6 myelinated axons; compression: 78.9+/-13.8; atraumatic: 0), increased Schwann cell proliferation (epineurotomy: 72.2% increase; compression: 39% increase) and cAMP response-element binding protein expression at the expense of a net deficit in donor axon counts distal to the repair. These differences were manifest by 150 days, at which point quantitative evidence for pruning was obtained. We conclude that ETS repair relies upon injury to the donor nerve.
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Experimental neurology · Jun 2008
Comparative StudyIn vivo imaging of seizure activity in a novel developmental seizure model.
The immature brain is exceptionally susceptible to seizures. However, it remains unclear whether seizures occurring during development affect critical processes underlying neural circuit formation, leading to long-term functional consequences. Here we characterize a novel in vivo model system of developmental seizures based on the transparent albino Xenopus laevis tadpole, which allows direct examination of seizure activity, and seizure-induced effects on neuronal development within the intact unanesthetized brain. ⋯ Similar to other developmental seizure models, prolonged seizures failed to induce marked neuronal death within the brain, detected by cellular propidium iodide incorporation in vivo or TUNEL labeling. This novel developmental seizure model system has distinct advantages for controlled seizure induction, and direct visualization of both seizure activity and seizure-induced effects on individual developing neurons within the intact unanesthetized brain. Such a system is necessary to address important questions relating to the long-term impact of common perinatal seizures on developing neural circuits.
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Experimental neurology · Jun 2008
Comparative StudyCommunicating hydrocephalus in adult rats with kaolin obstruction of the basal cisterns or the cortical subarachnoid space.
Communicating hydrocephalus (CH) occurs frequently, but clinically-relevant animal models amenable to diagnostic imaging and cerebrospinal fluid shunting are not available. In order to develop and characterize models of subarachnoid space (SAS) obstruction at the basal cisterns (BC) or cerebral convexities (CX), 25% kaolin was injected in adult female Sprague-Dawley rats following halothane anesthesia; intact- or saline-injected animals served as controls. For BC animals (n=28 hydrocephalics, n=20 controls), an anterior approach to the C1-clivus interval was employed and 30 microl of kaolin or saline was injected. ⋯ Surprisingly, ventriculomegaly following CX injections was less severe and much more protracted, requiring 3-4 months to develop compared to ventriculomegaly produced by BC obstruction. No hydrocephalic animals demonstrated obvious neurological deficits, but BC-injected animals that subsequently developed more severe ventriculomegaly exhibited nasal discharges and "coughing" for several days following kaolin injection. The new BC model is relevant because the clinical presentation of CH in children is often associated with obstruction at this site, while the CX model may be more representative of late adult onset normal pressure hydrocephalus.