Abstract
Calcium dysfunction is involved in secondary traumatic brain injury (TBI). Manganese-enhanced MRI (MEMRI), in which the manganese ion acts as a calcium analog and a MRI contrast agent, was used to study rats subjected to a controlled cortical impact. Comparisons were made with conventional T2 MRI, sensorimotor behavior, and immunohistology. The major findings were: (1) Low-dose manganese (29 mg/kg) yielded excellent contrast with no negative effects on behavior scores relative to vehicle; (2) T1-weighted MEMRI was hyperintense in the impact area at 1-3 h, hypointense on day 2, and markedly hypointense with a hyperintense area surrounding the core on days 7 and/or 14, in contrast to the vehicle group, which did not show a biphasic profile; (3) in the hyperacute phase, the area of hyperintense T1-weighted MEMRI was larger than that of T2 MRI; (4) glial fibrillary acidic protein staining revealed that the MEMRI signal void in the impact core and the hyperintense area surrounding the core on day 7 and/or 14 corresponded to tissue cavitation and reactive gliosis, respectively; (5) T2 MRI showed little contrast in the impact core at 2 h, hyperintense on day 2 (indicative of vasogenic edema), hyperintense in some animals but pseudonormalized in others on day 7 and/or 14; (6) behavioral deficit peaked on day 2. We concluded that MEMRI detected early excitotoxic injury in the hyperacute phase, preceding vasogenic edema. In the subacute phase, MEMRI detected contrast consistent with tissue cavitation and reactive gliosis. MEMRI offers novel contrasts of biological processes that complement conventional MRI in TBI.