title: Traumatic brain injury causes an FK506-sensitive loss and an overgrowth of dendritic spines in rat forebrain.
abstract: Traumatic brain injury (TBI) causes both an acute loss of tissue and a progressive injury through reactive processes such as excitotoxicity and inflammation. These processes may worsen neural dysfunction by altering neuronal circuitry beyond the focally-damaged tissue. One means of circuit alteration may involve dendritic spines, micron-sized protuberances of dendritic membrane that support most of the excitatory synapses in the brain. This study used a modified Golgi-Cox technique to track changes in spine density on the proximal dendrites of principal cells in rat forebrain regions. Spine density was assessed at 1 h, 24 h, and 1 week after a lateral fluid percussion TBI of moderate severity. At 1 h after TBI, no changes in spine density were observed in any of the brain regions examined. By 24 h after TBI, however, spine density had decreased in ipsilateral neocortex in layer II and III and dorsal dentate gyrus (dDG). This apparent loss of spines was prevented by a single, post-injury administration of the calcineurin inhibitor FK506. These results, together with those of a companion study, indicate an FK506-sensitive mechanism of dendritic spine loss in the TBI model. Furthermore, by 1 week after TBI, spine density had increased substantially above control levels, bilaterally in CA1 and CA3 and ipsilaterally in dDG. The apparent overgrowth of spines in CA1 is of particular interest, as it may explain previous reports of abnormal and potentially epileptogenic activity in this brain region.
authors.affiliation: Department of Anatomy & Neurobiology, Virginia Commonwealth University, Richmond, Virginia, USA.
authors.forename: John N
authors.initials: JN
authors.lastname: Campbell
authors.forename: David
authors.initials: D
authors.lastname: Register
authors.forename: Severn B
authors.initials: SB
authors.lastname: Churn
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D001930:Brain Injuries / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D049229:Dendritic Spines / Q000187:drug effects / Q000473:pathology*; D004195:Disease Models, Animal; D008297:Male; D009410:Nerve Degeneration / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016559:Tacrolimus / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D016559:Tacrolimus