Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
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J. Cereb. Blood Flow Metab. · Apr 2005
Neuroprotective efficacy of repinotan HCl, a 5-HT1A receptor agonist, in animal models of stroke and traumatic brain injury.
Repinotan is a highly potent 5-HT1A receptor agonist with strong neuroprotective efficacy in animal models of middle cerebral artery occlusion and traumatic brain injury. In this study, we characterized the time window for neuroprotective effects of repinotan in animal models. In the permanent middle cerebral artery occlusion model, repinotan showed neuroprotective efficacy when administered as a triple bolus injection (0.3-100 microg/kg) or an intravenous infusion (0.3-100 microg/kg per hour). ⋯ In the acute subdural hematoma model, repinotan (3 and 10 microg/kg per hour) reduced infarct volume by 65%. In this model, repinotan (3 microg/kg per hour) administered 5 hours after occlusion reduced infarct volume by 54%. The favorable neuroprotective efficacy, broad dose-response curve, and prolonged therapeutic window observed in all models strongly suggest that repinotan is a promising candidate for treating acute ischemic stroke in humans.
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J. Cereb. Blood Flow Metab. · Mar 2005
Clinical TrialTracer delay correction of cerebral blood flow with dynamic susceptibility contrast-enhanced MRI.
Cerebral blood flow (CBF) and vascular mean transit time (MTT) can be determined by dynamic susceptibility contrast-enhanced magnetic resonance imaging and deconvolution with an arterial input function. However, deconvolution by a singular value decomposition (SVD) method is sensitive to the tracer delay that often occurs in patients with cerebrovascular disease. We investigated the effect of tracer delay on CBF determined by SVD deconvolution. ⋯ We applied the delay correction to the CBF and MTT images acquired for nine patients with hyperacute stroke and unilateral occlusion of the middle cerebral artery. We found in some patients that the delay correction modulated the contrast of CBF and MTT images. For hyperacute stroke patients, tracer delay correction is essential to obtain reliable perfusion image when SVD deconvolution is used.
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J. Cereb. Blood Flow Metab. · Feb 2005
Development of posttraumatic hyperthermia after traumatic brain injury in rats is associated with increased periventricular inflammation.
Posttraumatic hyperthermia (PTH) is a noninfectious elevation in body temperature that negatively influences outcome after traumatic brain injury (TBI). We sought to (1) characterize a clinically relevant model and (2) investigate potential cellular mechanisms of PTH. In study I, body temperature patterns were analyzed for 1 week in male rats after severe lateral fluid percussion (FP) brain injury (n=75) or sham injury (n=17). ⋯ In study II, a separate group of animals underwent the same injury and temperature monitoring paradigm as in study I, but had additional physiologic data obtained, including vital signs, arterial blood gases, white blood cell counts, and C-reactive protein levels. All parameters remained within normal ranges after injury. These data suggest that PTH and the alteration in CR of temperature may be due, in part, to acute reactive astrocytosis and inflammation in hypothalamic centers responsible for both thermoregulation and CR.
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J. Cereb. Blood Flow Metab. · Dec 2004
Cerebral vascular and metabolic response to sustained systemic inflammation in ovine traumatic brain injury.
Traumatic brain injury (TBI) is frequently accompanied by a systemic inflammatory response secondary to multiple trauma, shock, or infections. This study investigated the impact of sustained systemic inflammation on cerebral hemodynamics and metabolism in ovine traumatic brain injury. Fifteen sheep were investigated for 14 hours. ⋯ The CMRO2, PaCO2, and arterial hematocrit values were identical among the groups between 10 and 14 hours. It is concluded that chronic endotoxemia in ovine traumatic brain injury was associated with cerebral vasodilation uncoupled from global brain metabolism. Different mechanisms appear to induce cerebral vasodilation in response to inflammation and hypercapnia.
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J. Cereb. Blood Flow Metab. · Dec 2004
Functional magnetic resonance imaging and somatosensory evoked potentials in rats with a neonatally induced freeze lesion of the somatosensory cortex.
Brain plasticity is an important mechanism for functional recovery from a cerebral lesion. The authors aimed to visualize plasticity in adult rats with a neonatal freeze lesion in the somatosensory cortex using functional magnetic resonance imaging (fMRI), and hypothesized activation outside the primary projection area. A freeze lesion was induced in the right somatosensory cortex of newborn Wistar rats (n = 12). ⋯ SSEPs were distorted and smaller in amplitude, and fMRI activation was significantly weaker in the lesioned hemisphere. Only in a few animals were cortical areas outside the primary sensory cortex activated. The results are discussed in respect to an apparent absence of plasticity, loss of excitable tissue, the excitability of the lesioned hemisphere, altered connectivity, and a disturbed coupling of increased neuronal activity to the hemodynamic response.