Abstracts

Mn²⁺ is a paramagnetic ion commonly exploited in Mn²⁺ -enhanced MRI (MEMRI). Mn²⁺ mimics Ca²⁺ and is taken up by living neurons, transported by axons across synapses, and can reflect functional properties of neuronal connections. We have used MEMRI to investigate the mossy fiber pathway in the kainic acid model of temporal lobe epilepsy. It was anticipated that MEMRI would reveal reorganization of mossy fibers during epileptogenesis [italic]in vivo[/italic], and consequently, be used as a candidate surrogate marker for development of epilepsy. Status epilepticus (SE) was induced with kainic acid (11 mg/kg, i.p.) in 5 adult male Wistar rats. Controls (n=6) received saline. Two weeks later, injections of Mn[sub]2[/sub]Cl (1M, 30-50 nl) were targeted to the caudal subfield of the entorhinal cortex (EC). MRI data was acquired 3, 5, 7, 9, and 10 d after MnCl[sub]2[/sub] injection using a 4.7T magnet interfaced to a Varian console. T[sub]1[/sub]-weighted (TE=2.7 ms, TR=120 ms, flip=70 deg) 3D gradient echo MRI was performed. A volume of 25*25*35 mm³ was covered with 192*64*256 points. Signal intensities of the regions of interest were measured and normalized with adjacent muscle tissue. AVS Express software was used to create volume rendered 3D reconstructions from volumes enhanced by Mn²⁺. After MRI, animals were perfused with Timm fixation to verify mossy fiber sprouting. All animals with SE developed spontaneous seizures within 3 weeks. In controls, MEMRI signal was detected in all subfields of hippocampus. In epileptic rats, signal was stronger than in controls in hilus and CA3 subfield, probably related to mossy fiber sprouting that was verified by histology. Unexpectedly, epileptic animals also had stronger MEMRI signal in the laterodorsal thalamus which may be due to spread of tracer substance to postrhinal cortex at the time of injection. Both in controls and epileptic animals the MEMRI signal enhancement was more pronounced ipsilaterally than contralaterally. Our data indicates that the MRI detectable trans-neuronal tracer, Mn²⁺, was transported from the EC via the perforant pathway to the granule cells of dentate gyrus resulting in the labeling of mossy fibers. Consequently, we could non-invasively detect an increase in the extent of mossy fiber pathway in epileptic brain. Our data also provide the first evidence that target cells of the postrhinal cortex-thalamus pathway may undergo reorganization during epileptogenesis. (Supported by Academy of Finland, Sigrid Juselius Foundation)