Training of the impaired forelimb after traumatic brain injury enhances hippocampal neurogenesis in the Emx1 null mice lacking a corpus callosum.
Unilateral brain injury is known to disrupt the balance between the two cortices, as evidenced by an abnormally high interhemispheric inhibitory drive from motor cortex M1intactto M1lesionedtransmitted transcallosally. Our previous work has shown that the deletion of homeobox gene Emx1 not only led to the agenesis of the corpus callosum (cc), but also to reduced hippocampal neurogenesis. The current study sought to determine whether lacking the cc affected the recovery of forelimb function and hippocampal plasticity following training of the affected limb in mice with unilateral traumatic brain injuries (TBI). One week after TBI, produced by a controlled cortical impact to impair the preferred limb, Emx1 wild type (WT) and knock out (KO) mice were subjected to the single-pellet reaching task with the affected limb for 4 weeks. Both TBI and Emx1 deletion had overall adverse effects on the successful rate of reaching. However, TBI significantly affected reaching performance only in the WT mice and not in the KO mice. Both TBI and Emx1 gene deletion also negatively affected hippocampal neurogenesis, demonstrated by a reduction in doublecortin (DCX)-expressing immature neurons, while limb training enhanced DCX expression. However, limb training increased DCX cells in KO mice only in the TBI-treated group, whereas it induced neurogenesis in both WT mice groups regardless of the treatment. Our finding also suggests that limb training enhances neuroplasticity after brain injury at functionally remote regions including the hippocampus, which may have implications for promoting overall recovery of function after TBI.
San Francisco Veteran's Affairs Medical Center, University of California San Francisco, San Francisco, CA 94121, USA; Departments of Neurological Surgery, University of California San Francisco, San Francisco, CA 94158, USA.
Melanie
M
Neumann
San Francisco Veteran's Affairs Medical Center, University of California San Francisco, San Francisco, CA 94121, USA; Departments of Neurological Surgery, University of California San Francisco, San Francisco, CA 94158, USA; Department of Neurological Surgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
Wei
W
Liu
San Francisco Veteran's Affairs Medical Center, University of California San Francisco, San Francisco, CA 94121, USA; Departments of Neurological Surgery, University of California San Francisco, San Francisco, CA 94158, USA; Department of Neurological Surgery, Second Affiliated Hospital of Zhejiang University Medical College, Hangzhou, China.
Chongran
C
Sun
San Francisco Veteran's Affairs Medical Center, University of California San Francisco, San Francisco, CA 94121, USA; Departments of Neurological Surgery, University of California San Francisco, San Francisco, CA 94158, USA.
Shih Yen
SY
Yang
Departments of Neurological Surgery, University of California San Francisco, San Francisco, CA 94158, USA; Physical Therapy and Rehabilitation Science, University of California San Francisco, San Francisco, CA 94121, USA.
Linda J
LJ
Noble-Haeusslein
San Francisco Veteran's Affairs Medical Center, University of California San Francisco, San Francisco, CA 94121, USA; Departments of Neurological Surgery, University of California San Francisco, San Francisco, CA 94158, USA. Electronic address: jialing.liu@ucsf.edu.
Jialing
J
Liu
D061085:Agenesis of Corpus Callosum / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D000070642:Brain Injuries, Traumatic / Q000150:complications* / Q000473:pathology / Q000503:physiopathology / Q000534:rehabilitation*; D004195:Disease Models, Animal; D000089662:Doublecortin Protein; D005552:Forelimb / Q000503:physiopathology*; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology*; D018398:Homeodomain Proteins / Q000235:genetics; D008297:Male; D018345:Mice, Knockout; D009048:Motor Skills / Q000502:physiology; D055495:Neurogenesis / Q000502:physiology; D000066530:Neurological Rehabilitation; D009473:Neuronal Plasticity / Q000502:physiology; D011897:Random Allocation; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics; D000099260:Empty Spiracles Homeobox Proteins
D000089662:Doublecortin Protein; D018398:Homeodomain Proteins; D014157:Transcription Factors; D000099260:Empty Spiracles Homeobox Proteins; C000714847:Dcx protein, mouse
Controlled cortical impact; DCX; Emx1; Neuroplasticity; Skill reaching