The behavioral and histological effects of the lateral fluid percussion (LFP) brain injury model were compared with the weight drop impact-acceleration model with 10 min of secondary hypoxia (WDIA + H). LFP injury resulted in significant motor deficits on the beam walk and inclined plane, and memory deficits on the radial arm maze and Morris water maze. Motor deficits following LFP remained throughout 6 weeks of behavioral testing. WDIA + H injury produced significant motor deficits on the beam walk and inclined plane immediately following injury, but these effects were transient and recovered by 14 days post-injury. In contrast to the LFP injury, the WDIA + H injured animals showed no memory deficits on the radial arm maze and Morris water maze. In order to determine if the differences in behavioral outcome between models were due to differences in injury mechanism or injury severity, 10 LFP-injured animals were matched with 10 WDIA-injured animals based on injury severity (i.e., time to regain righting reflex after brain injury). The LFP-matched injury group showed greater impairment than the WDIA + H matched injury group on the radial arm maze and Morris water maze. Histological examination of LFP-injured brains with Fluoro-Jade staining 24 h, 48 h, and 7 days post-injury revealed degenerating neurons in the cortex, thalamus, hippocampus, caudate-putamen, brainstem, and cerebellum, with degenerating fibers tracts in the corpus callosum and other major tracts throughout the brain. Fluoro-Jade staining following WDIA+H injury revealed damage to fibers in the optic tract, lateral olfactory tract, corpus callosum, anterior commissure, caudate-putamen, brain stem, and cerebellum. While both models produce reliable and characteristic behavioral and neuronal pathologies, their differences are important to consider when choosing a brain injury model.

Estradiol mediates structural changes at synapses of the hippocampus, an area in the brain important for learning and memory. This study was designed to test the hypothesis that estradiol mediates subcellular changes of synaptic proteins to induce new synapses via an estrogen receptor (ER)-mediated process. To elucidate the mechanisms involved in glutamatergic synapse formation, we investigated effects of estradiol on synaptic proteins in cultured hippocampal neurons using immunocytochemistry and confocal microscopy. Synaptic protein distribution and size were identified with antibodies to the presynaptic vesicular glutamate transporter protein (vGlut1) and postsynaptic NMDA receptor (NR1 subunit). We observed an increase in synapse density, as detected by NR1 and vGlut1 colocalization, along dendrites of neurons cultured in steroid-stripped media and exposed to estradiol (10 nM) for 48 h. Additionally, the NR1 subunit was enriched at synaptic clusters. Immunocytochemistry and confocal imaging revealed punctate staining of extranuclear ERs along dendrites of hippocampal neurons expressing NR1. Estradiol increased the density of both ER-␣ and ER-␤ protein clusters along dendrites. To test whether ERs

Traditionally, astrocytes have been considered less susceptible to injury than neurons. Yet, we have recently shown that astrocyte death precedes neuronal death in a rat model of traumatic brain injury (TBI) (Zhao et al.: Glia 44:140-152, 2003). A main mechanism hypothesized to contribute to cellular injury and death after TBI is elevated intracellular calcium ([Ca 2+ ] i ). Since calcium regulation is also influenced by regulation of intracellular sodium ([Na + ] i ), we used an in vitro model of strain-induced traumatic injury and live-cell fluorescent digital imaging to investigate alterations in [Na + ] i in cortical astrocytes after injury. Changes in [Na + ] i , or [Ca 2+ ] i were monitored after mechanical injury or L-glutamate exposure by ratiometric imaging of sodiumbinding benzofuran isophthalate (SBFI-AM), or Fura-2-AM, respectively. Mechanical strain injury or exogenous glutamate application produced increases in [Na + ] i that were dependent on the severity of injury or concentration. Injury-induced increases in [Na + ] i were significantly reduced, but not completely eliminated, by inhibition of glutamate uptake by DL-threo-β-benzyloxyaspartate (TBOA). Blockade of sodium-dependent calcium influx through the sodiumcalcium exchanger with 2-[2-[4-(4-Nitrobenzyloxy)-phenyl]ethyl]isothiourea mesylate (KB-R7943) reduced [Ca 2+ ] i after injury. KB-R7943 also reduced astrocyte death after injury. These findings suggest that in astrocytes subjected to mechanical injury or glutamate excitotoxicity, increases in intracellular Na + may be a critical component in the injury cascade and a therapeutic target for reduction of lasting deficits after traumatic brain injury.