Mild hypothermia prevents post-traumatic hyperactivity of excitatory synapses in rat hippocampal CA1 pyramidal neurons.
ABSTRACT The present experiment examined the effect of mild hypothermia (35 degrees C) on the post-traumatic hyperactivity of rat hippocampal CA1 neurons in horizontal brain slices. One week after fluid percussion injury (FPI), the optical response evoked by stimulation of the Schaffer collaterals increased in amplitude and propagation area in hippocampal CA1 slices. FPI did not alter the fast optical response that reflected the action potential of the Schaffer collaterals but enhanced the slow component that reflected the excitatory postsynaptic response. FPI increased the slope of the input-output relation (I/O function), suggesting that FPI increases the efficacy of excitatory synaptic transmission in the hippocampal CA1 pyramidal neurons. To examine the effect of low temperature on post-traumatic hyperactivity of hippocampal CA1 neurons, mild hypothermia (35 degrees C) was administered to rats 15 min after FPI and maintained for 1-3 h. One week after FPI, the activity of hippocampal CA1 neurons in rats with mild hypothermia appeared to be reduced as compared with those receiving FPI alone. The post-traumatic enhancement of the I/O function of the slow optical response was prevented by mild hypothermia. These results suggest that mild hypothermia applied 15 min after FPI attenuates the post-traumatic hyperactivity of excitatory synapses in rat hippocampal CA1 neurons.
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ABSTRACT: Evidence shows that artificially lowering body and brain temperature can significantly reduce the deleterious effects of brain injury in both newborns and adults. Although the benefit of therapeutic hypothermia have long been known and applied clinically, the underlying molecular mechanisms have yet to be elucidated. Hypoxic-ischemic brain injury and traumatic brain injury both trigger a series of biochemical and molecular events that cause additional brain insult. Induction of therapeutic hypothermia seems to ameliorate the molecular cascade that culminates in neuronal damage. Hypothermia attenuates the toxicity produced by the initial injury that would normally produce reactive oxygen species, neurotransmitters, inflammatory mediators, and apoptosis. Experiments have been performed on various depths and levels of hypothermia to explore neuroprotection. This review summarizes what is currently known about the beneficial effects of therapeutic hypothermia in experimental models of neonatal hypoxic-ischemic brain injury and traumatic brain injury, and explores the molecular mechanisms that could become the targets of novel therapies. In addition, this review summarizes the clinical implications of therapeutic hypothermia in newborn hypoxic-ischemic encephalopathy and adult traumatic brain injury.Current Molecular Medicine 07/2012; DOI:10.2174/156652412803833517 · 3.61 Impact Factor
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ABSTRACT: Recent reports suggest that experiencing a mild closed head trauma or mild traumatic brain injury (mTBI) is associated with a greater incidence of anxiety disorders. Dysfunction of limbic structures, such as the medial prefrontal cortex, amygdala and hippocampus, is associated with the symptoms of anxiety disorders. Therefore, the goal of the current studies was to characterize the consequences of closed mTBI on these limbic structures and associated fear and anxiety-related behaviors. A weight-drop procedure was employed to induce mTBI in male rats. Rats were transcardically perfused 4 or 9 days following exposure to mTBI or control procedures, and neuronal number, brain region area, and the number of apoptotic cells in each region were determined. In separate groups of rats, the effects of mTBI on anxiety-like behaviors, motor function, nociception, and acquisition, retention and extinction of contextual fear were also assessed. Findings suggest that mTBI was associated with significant neuronal cell loss in the CA1 region of the dorsal hippocampus and increased cell number in subregions of the amygdala, both of which appear to be related to alterations to apoptosis in these regions following mTBI. Furthermore, mTBI increased expression of anxiety-like behaviors and conditioned fear, with no effect on motor performance or nociception. Overall, a single impact to the skull to mimic mTBI in rats produces discrete alterations to neuronal numbers within the limbic system and specific emotional deficits, providing a potential neurobiological link between mTBI and anxiety disorders.Experimental Neurology 04/2012; 235(2):574-87. DOI:10.1016/j.expneurol.2012.03.012 · 4.62 Impact Factor