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Traumatic Brain Injury and Hippocampal Plasticity: Enhanced Recovery of Function with (±) Z‐Bisdehydrodoisynolic Acid [(±)‐Z‐BDDA] Parallels Increased Neurogenesis in Dentate Gyrus
Author(s) -
Clough Rich,
Neese S.L.,
Yan X.X.,
Xiong K.,
Banz W.J.,
Modglin A.A.,
Meyers C.Y.,
Hou Y.,
Smith D.C.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a879
Subject(s) - hippocampal formation , neurogenesis , dentate gyrus , morris water navigation task , doublecortin , traumatic brain injury , hippocampus , neuroplasticity , medicine , neuroscience , neun , endocrinology , psychology , anesthesia , immunohistochemistry , psychiatry
Cortical Contusion Injury (CCI) is an experimental model of traumatic brain injury (TBI). After CCI, rats show deficits in motor performance, reference memory, sensorimotor acquisition tasks and altered hippocampal plasticity. We have reported that a “seco‐steroid” (±)‐Z‐BDDA, has potent estrogenic and antioxidant effects and significantly enhances recovery of function following CCI in rats. The present study sought to determine if (±)‐Z‐BDDA changes hippocampal neurogenesis that occurs after TBI. Anesthetized young adult male rats received stereotaxic CCI, followed by (±)‐Z‐BDDA (0.3 μg/g BW) or vehicle (sc) at 2, 24, and 48 h. Behavioral tests were performed for two weeks followed by autopsy and doublecortin (DBX) staining. Treatment with (±)‐Z‐BDDA after CCI significantly improved Morris water‐maze performance two weeks after injury. These findings were paralleled by a robust and significant increase in hippocampal neurogenesis as determined by DBX staining and quantitative densitometry. These data suggest that recovery of function and hippocampal plasticity after CCI are simultaneously facilitated by (±)‐Z‐BDDA. Supported by NIH 5 R01 NS04155 and SIUSOM CRC funds.