Experimental neurology
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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.
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Experimental neurology · May 2008
Delayed treatment of spinal cord injury with erythropoietin or darbepoetin--a lack of neuroprotective efficacy in a contusion model of cord injury.
A number of drugs commonly used for a variety of clinical indications have been found recently to have substantial neuroprotective properties, raising the potential for rapid translation into human clinical trials of spinal cord injury (SCI). In this study we compared the neuroprotective efficacy of erythropoietin and a derivative of it, darbepoetin, in an acute model of thoracic SCI. Sprague-Dawley rats were randomized to receive erythropoietin (5000 IU/kg), darbepoetin (10 mug/kg), or saline, as a single intravenous injection 1 h after a thoracic contusion SCI. ⋯ Furthermore, no differences were observed in grey or white matter sparing between the three experimental groups. Using doses of erythropoietin and darbepoetin that other investigators have reported to be beneficial in SCI and stroke models, we were unable to demonstrate a neuroprotective effect when administered 1 h after injury. Further preclinical investigation is necessary to refine the treatment strategy of using erythropoietin or darbepoetin in acute spinal cord injury.
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Experimental neurology · May 2008
Modest spontaneous recovery of ventilation following chronic high cervical hemisection in rats.
Following C2 spinal hemisection (C2HS) in adult rats, ipsilateral phrenic motoneuron (PhMN) recovery occurs through a time-dependent activation of latent, crossed-spinal collaterals (i.e., spontaneous crossed phrenic phenomenon; sCPP) from contralateral bulbospinal axons. Ventilation is maintained during quiet breathing after C2HS, but the ability to increase ventilation during a respiratory stimulation (e.g. hypercapnia) is impaired. We hypothesized that long-term expression of the sCPP would correspond to a progressive normalization in ventilatory patterns during respiratory challenge. ⋯ We also noted that phrenic neurograms demonstrated a consistent delay in onset of the ipsilateral vs. contralateral inspiratory phrenic burst at 2-12-week post-injury. Finally, the ipsilateral phrenic response to respiratory challenge (hypoxia) was greater, though not normalized, at 4-12- vs. 2-week post-injury. We conclude that recovery of ventilation deficits occurs over 2-12-week post-C2HS; however, intrinsic neuroplasticity remains insufficient to concurrently restore a normal level of ipsilateral phrenic output.