Journal of neurotrauma
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Journal of neurotrauma · May 2003
Increased hippocampal CA3 vulnerability to low-level kainic acid following lateral fluid percussion injury.
This study was designed to determine whether a secondary increase in neuronal activity induced by a low dose of kainic acid (KA), a glutamate analogue, exacerbates the anatomical damage in hippocampal regions following a mild lateral fluid percussion (LFP) brain injury. KA (9 mg/kg) was injected intraperitoneally in LFP-injured rats (n = 16) 1 h post-trauma. The neuronal loss in the CA3, CA4, and hilar regions at 7 days was quantified by two-dimensional cell counts. ⋯ No changes were found in the BBB permeability as measured by [(14)C]aminoisobutyric acid in CA3, CA4, and hilar regions. We conclude that the presence of low-level KA 1 h after LFP dramatically increases the extent of hippocampal activation and induces a striking loss of ipsilateral CA3 and CA4 pyramidal neurons. Neuronal excitation during a time of cellular vulnerability may trigger or amplify the cycle of secondary damage in functionally impaired, but potentially viable, tissue.
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Journal of neurotrauma · Apr 2003
Transient neuronal but persistent astroglial activation of ERK/MAP kinase after focal brain injury in mice.
Astrogliosis is a nearly ubiquitous response to a variety of insults to the central nervous system (CNS). This reaction is triggered rapidly, but can persist for years after the initial trauma. Little is known about the signaling mechanisms responsible for this activation and its chronic maintenance. ⋯ However, pERK-positive astrocytes represented only a subset of total GFAP-positive cells and were found more proximal to the lesion suggesting specific functional activation of these cells. Finally, immunostaining for the phosphorylated form of cAMP response element-binding (CREB) protein, a downstream target of the ERK/MAPK cascade, was increased in perilesional glia 7 d after FSL. Sustained activation of the ERK/MAPK signaling pathway in perilesional reactive glia suggests a critical role for this cascade in astrogliosis.
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Journal of neurotrauma · Apr 2003
Posttraumatic hypothermia followed by slow rewarming protects the cerebral microcirculation.
In the clinical and laboratory setting, multiple reports have suggested the efficacy of hypothermia in blunting the damaging consequences of traumatic brain injury (TBI). With the use of posttraumatic hypothermia, it has been recognized that the time of initiation and duration of hypothermia are important variables in determining the degree of neuroprotection provided. Further, it has been recently recognized that the rate of posttraumatic rewarming is an important variable, with rapid rewarming exacerbating neuronal/axonal damage in contrast to slow rewarming which appears to provide enhanced neuroprotection. ⋯ Through this approach, it was found that posttraumatic hypothermia followed by slow rewarming maintained normal arteriolar vascular responses in terms of ACh-dependent dilation and CO2 reactivity. In contrast, arterioles subjected to TBI followed by normothermia or hypothermia and rapid rewarming showed impaired vasoreactivity in terms of their ACh-dependent and CO2 responses. This study provides additional evidence of the benefits of posttraumatic hypothermia followed by slow rewarming, demonstrating for the first time that the previously described neuroprotective effects extend to the cerebral microcirculation.
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Journal of neurotrauma · Apr 2003
Effects of LY379268, a selective group II metabotropic glutamate receptor agonist on EEG activity, cortical perfusion, tissue damage, and cortical glutamate, glucose, and lactate levels in brain-injured rats.
Activating presynaptic group II metabotropic glutamate (mGlu II) receptors reduces synaptic glutamate release. Attenuating glutamatergic transmission without blocking ionotropic glutamate receptors, thus avoiding unfavorable psychomimetic side effects, makes mGlu II receptor agonists a promising target in treating brain-injured patients. Neuroprotective effects of LY379268 were investigated in rats following controlled cortical impact injury (CCI). ⋯ Cortical glutamate, glucose, and lactate were not influenced. Significant reductions in EEG activity and contusion volume by LY379268 do not appear mediated by attenuated excitotoxicity and energetic impairment. Overall, an additional decrease in cortical perfusion seems to interfere with the anti-edematous potential of LY379268 during the early period following CCI, while an increase in perfusion in LY379268-treated rats at 7 days might contribute to tissue protection.
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Journal of neurotrauma · Apr 2003
Tempol, a novel stable nitroxide, reduces brain damage and free radical production, after acute subdural hematoma in the rat.
Recent studies have shown that there is increased production of deleterious free radicals following acute subdural hematoma (ASDH). Scavenging them may therefore be of therapeutic benefit. Nitroxides are new, low molecular weight, cell permeable superoxide dismutase mimics. ⋯ However, in Tempol-treated animals, this early surge was attenuated, and all measured values remained around the baseline levels throughout the experiments. Tempol thus provides significant neuroprotective effect in a rat model of ASDH, related to attenuation of superoxide radical production. The use of these low molecular weight, cell-permeable agents, which readily cross the blood-brain barrier and enter cells, thus appears indicated for acute pathologies, ASDH.