Abstracts

Mn²⁺-enhanced magnetic resonance imaging (MEMRI) can reveal functional, structural, and connectional alterations in the brain with a high spatial resolution [italic]in vivo[/italic]. We showed that Mn²⁺ injected in the entorhinal cortex is transported via perforant pathway to the dentate granule cells resulting in labeling that correlates with the density of mossy fiber sprouting [Nairismägi et al. Neuroimage 2006]. Now we hypothesized that systemic Mn injection and MEMRI can be used for detection of mossy fiber sprouting., MnCl[sub]2[/sub] (45mg/kg) was injected intraperitoneally to 10 adult Wistar rats. After 12 hours, status epilepticus (SE) was induced with kainic acid (KA) in 6 rats (MnSE group). T[sub]1[/sub] weighted (gradient echo, TE=2.7ms, TR=120ms) and quantitative T[sub]1[/sub] mapping (IR- fast spin echo, TI=10, 400, 1000, 1600 ms ) MRI was performed under 1% halothane anaesthesia at 4.7T, 3 and 25 hours after KA injection. Two months later, follow-up MRI was performed before and 24 hours after injection of Mn. In the end, rats were perfused for histology, and brains were stained to detect neurodegeneration, gliosis, and mossy fiber sprouting., At 15 h after KA injection, T[sub]1[/sub] relaxation times did not differ between the groups. This indicates that Mn accumulation during generalized seizures is not activity dependent. Two months after KA administration, Mn-enhanced MRI indicated thickening of the dentate gyrus (DG) and proximal CA3 in T[sub]1[/sub]-weighted images in the MnSE group (260[plusmn]40 % increase compared to controls, p[lt]0.05). The CA1/adjacent corpus callosum signal intensity was 1.37 [plusmn] 0.03 in the MnSE and 1.22[plusmn]0.03 in the control group (Fig. 1, p[lt]0.05), confirming the increased accumulation of Mn in the CA1 region of the KA-injected animals. The initial histological analysis shows both mossy fiber sprouting (DG) and neuronal loss related gliosis (CA1) in the signal enhancement areas.[figure1]Fig.1 Manganase enhanced T[sub]1[/sub]-wt images 25h (A,C) and 2 months after KA injection from two representative animals., MEMRI contrast after systemic Mn injection is not associated with brain activation during and after SE. Alterations in the thickness and shape of the DG and CA3 or CA1 regions of hippocampus proper can be attributed either to mossy fiber sprouting or gliosis, respectively. According to our data it is evident that MEMRI after systemic administration is able to reveal cellular level changes in the hippocampus. It remains to be studied if the accumulation of Mn into mossy fibers and/or glia can be differentiated., (Supported by Finnish Cultural Foundation of Northern Savo.)