Examining behavioral and astrocytic phenotypes in spinal cord injury research

Rehabilitation is used to help patients with spinal cord injuries (SCI) retain and strengthen remaining motor control. Patients with cervical SCI often develop tetraplegia, resulting in lost voluntary control of upper and lower extremities. Current studies using mouse models of SCI do not sufficiently utilize rehabilitative strategies to restore forelimb function. I first tested whether rehabilitative training improves functional recovery following an asymmetrical cervical-level injury that spares a small part the corticospinal tract. Our injury caused deficits in forelimb function that sustained for 12 weeks. Then I assessed the effect of rehabilitation on forelimb function on the staircase task. Forelimb rehabilitation initially accelerated functional recovery, but mice without rehabilitative training eventually caught up in the degree of recovery. These results indicate that rehabilitative training is useful in promoting functional recovery, but the degree of recovery is limited. The second part of my thesis involves the astrocytic response to SCI. An astrocytic scar forms after SCI and is often described as an obstacle to axon growth, but recent evidence suggests that it can also facilitate regeneration. Previous work from our lab has shown that Leucine zipper-bearing kinase (LZK, also called MAP3K13) positively regulates astrocyte reactivity. In collaboration with another lab member, we compared two variants of genetic overexpression of LZK: random insertion of an LZK overexpression construct into the mouse genome (GFAP-CreERT2; LZKOE) and site-specific integration of the same LZK construct into a safe harbor locus (GFAP-CreERT2; H11-LZKOE). Our goal was to determine whether the site specific line behaves similarly to the published random integration line in LZK-induced astrocyte reactivity. Tamoxifen induction of LZK overexpression in GFAP-CreERT2; H11-LZKOE mice is associated with higher incidence of weight loss and lethality, but seemingly higher astrocyte reactivity than the random integration line