Journal of neurotrauma
-
Journal of neurotrauma · Dec 2012
Repetitive mild traumatic brain injury in a mouse model produces learning and memory deficits accompanied by histological changes.
Concussion or mild traumatic brain injury (mTBI) represents the most common type of brain injury. However, in contrast with moderate or severe injury, there are currently few non-invasive experimental studies that investigate the cumulative effects of repetitive mTBI using rodent models. Here we describe and compare the behavioral and pathological consequences in a mouse model of single (s-mTBI) or repetitive injury (r-mTBI, five injuries given at 48 h intervals) administered by an electromagnetic controlled impactor. ⋯ Axonal injury, manifest as amyloid precursor protein immunoreactive axonal profiles, was present in the corpus callosum of both injury groups, though more evident in the r-mTBI animals. Our data demonstrate that this mouse model of mTBI is reproducible, simple, and noninvasive, with behavioral impairment after a single injury and increasing deficits after multiple injuries accompanied by increased focal and diffuse pathology. As such, this model may serve as a suitable platform with which to explore repetitive mTBI relevant to human brain injury.
-
In the clinical setting, skin temperature is both easily evaluated and useful in assessments of sympathetic dysfunction. The present study purposed to observe the serial skin temperature changes of both hindlimbs following several types of sciatic nerve injury (complete transection and ligation model [CTL], crush injury model [CRI], and chronic constriction injury model [CCI]) in Sprague-Dawley rats and, further, to delineate the possible mechanisms through various evaluation methods. The temperature differences between the intact and injured areas (ΔT) on the plantar surface and toes varied among the CTL, CRI, and CCI injury models during the acute stage (7 days post-injury). ⋯ The latency and amplitude of the compound muscle action potential (CMAP) in the involved plantar muscle was not found in the CTL group 4 weeks post-injury, but showed gradual restoration in the CRI and CCI models. Regression analysis revealed that the ΔT in the plantar area and toes were affected only by the CMAP amplitude in the involved plantar muscle; therefore, it can be said that the skin temperature on the injured area after sciatic nerve injury was influenced by the functional status of the involved muscle. Measurement of skin temperature can differentiate mild peripheral nerve injury from moderate-to-severe injuries, although its clinical significance might be limited.
-
Journal of neurotrauma · Dec 2012
Carvacrol together with TRPC1 elimination improve functional recovery after traumatic brain injury in mice.
Death of Central Nervous System (CNS) neurons following traumatic brain injury (TBI) is a complex process arising from a combination of factors, many of which are still unknown. It has been found that inhibition of transient receptor potential (TRP) channels constitutes an effective strategy for preventing death of CNS neurons following TBI. TRP channels are classified into seven related subfamilies, most of which are Ca(2+) permeable and involved in many cellular functions, including neuronal cell death. ⋯ To better define the type of the specific channel involved, the effect of carvacrol on the extent and speed of recovery after TBI was compared among mice lacking TRPC1, TRPC3, or TRPC5, relative to wild type controls. We found that neurological recovery after TBI was significantly enhanced by combining carvacrol with TRPC1 elimination, but not by the absence of TRPC3 or TRPC5, showing a synergistic effect between carvacrol application and TRPC1 elimination. We conclude that TRPC1-sensitive mechanisms are involved in TBI pathology, and that inhibition of this channel by carvacrol enhances recovery and should be considered for further studies in animal models and humans.
-
Journal of neurotrauma · Dec 2012
The frontal lobe and thalamus have different sensitivities to hypoxia-hypotension after traumatic brain injury: a microdialysis study in rats.
After traumatic brain injury (TBI), lesions are anatomically heterogeneous, but the spatial heterogeneity of the post-traumatic brain's vulnerability to hypoxia-hypotension (HH) has been poorly studied. Our objective was to compare the effect of HH after TBI on brain energy metabolism into two regions: the frontal lobe and the thalamus. Twenty-eight Sprague-Dawley rats were randomized into four groups: sham, TBI (brain trauma alone, impact acceleration, 450-g weight drop from 1.8 m), HH (blood depletion to mean arterial pressure 40 mm Hg, FiO(2) 10%, 15 min), and TBI-HH (TBI followed by HH, 45-min delay). ⋯ During the 30 min following the HH phase (reperfusion), an increase in PtiO(2) was observed. In the TBI-HH group, this increase was significantly lower in the frontal lobe than in the thalamus. These findings demonstrate that in the early post-traumatic period, the metabolic cerebral response to HH is higher in the frontal lobe than in the thalamus, and is worsened by TBI, suggesting a higher vulnerability for the frontal lobes.
-
Journal of neurotrauma · Nov 2012
Functional and histological outcome after focal traumatic brain injury is not improved in conditional EphA4 knockout mice.
We investigated the role of the axon guidance molecule EphA4 following traumatic brain injury (TBI) in mice. Neutralization of EphA4 improved motor function and axonal regeneration following experimental spinal cord injury (SCI). We hypothesized that genetic absence of EphA4 could improve functional and histological outcome following TBI. ⋯ TBI increased cortical and hippocampal astrocytosis (GFAP immunohistochemistry, p<0.05) and hippocampal sprouting (Timm stain, p<0.05) and induced a marked loss of hemispheric tissue (p<0.05). EphA4 cKO did not alter the histological outcome. Although our results may argue against a beneficial role for EphA4 in the recovery process following TBI, further studies including post-injury pharmacological neutralization of EphA4 are needed to define the role for EphA4 following TBI.