In the current study we examined the effects of training in adult rats with a cervical spinal cord injury (SCI). One group of rats received 6 weeks of training in a single pellet reaching task immediately after injury, while a second group did not receive training. Following this period changes in cortical levels of BDNF and GAP-43 were analysed in trained and untrained animals and in a group with training but no injury. In another group of rats, functional recovery was analysed in the reaching task and when walking on a horizontal ladder. Thereupon, the cortical forelimb area was electrophysiologically examined using micro-stimulation followed by tracing of the lesioned corticospinal tract (CST). We found that trained rats improved substantially in the reaching task, when compared to their untrained counterparts. Trained rats however, performed significantly worse with their injured forelimb when walking on a horizontal ladder. In parallel to the improved recovery in the trained task, we found that the cortical area where wrist movements could be evoked by micro-stimulation expanded in trained rats in comparison to both untrained and uninjured rats. Furthermore, collateral sprouting of lesioned CST fibres rostral to the injury was increased in trained rats. Post-injury training was also found to increase cortical levels of GAP-43 but not BDNF. In conclusion we show that training of a reaching task promotes recovery of the trained task following partial SCI by enhancing plasticity at various levels of the central nervous system (CNS), but may come at the cost of an untrained task.

The transmembrane protein deleted in colorectal cancer (DCC) and its ligand, netrin-1, regulate synaptogenesis during development, but their function in the mature central nervous system is unknown. Given that DCC promotes cell-cell adhesion, is expressed by neurons, and activates proteins that signal at synapses, we hypothesized that DCC expression by neurons regulates synaptic function and plasticity in the adult brain. We report that DCC is enriched in dendritic spines of pyramidal neurons in wild-type mice, and we demonstrate that selective deletion of DCC from neurons in the adult forebrain results in the loss of long-term potentiation (LTP), intact long-term depression, shorter dendritic spines, and impaired spatial and recognition memory. LTP induction requires Src activation of NMDA receptor (NMDAR) function. DCC deletion severely reduced Src activation. We demonstrate that enhancing NMDAR function or activating Src rescues LTP in the absence of DCC. We conclude that DCC activation of Src is required for NMDAR-dependent LTP and certain forms of learning and memory.

Prolonged hypothermia reduces ischemic brain injury, but its efficacy after intracerebral hemorrhagic (ICH) stroke is unresolved. Rats were implanted with core temperature telemetry probes and subsequently subjected to an ICH, which was produced by infusing bacterial collagenase into the striatum. Animals were kept normothermic (NORMO), or were made mildly hypothermic (33-35 degrees C) for over 2 days starting 1 hour (HYP-1), 6 hours (HYP-6), or 12 hours (HYP-12) after collagenase infusion. Others were cooled for 7 hours beginning 1 hour after infusion (BRIEF). Skilled reaching, walking, and spontaneous forelimb use were assessed. Normothermic ICH rats sustained, on average, a 36.9-mm3 loss of tissue at 1 month. Only the HYP-12 group had a significantly smaller lesion (25.5 mm3). Some functional improvements were found with this and other hypothermia treatments. Cerebral edema was observed in NORMO rats, and was not lessened significantly by hypothermia (HYP-12). Blood pressure measurements, as determined by telemetry, in BRIEF rats showed that hypothermia increased blood pressure. This BRIEF treatment also resulted in significantly more bleeding at 12 hours after ICH (79.2 microL) versus NORMO-treated rats (58.4 microL) as determined by a spectrophotometric hemoglobin assay. Accordingly, these findings suggest that early hypothermia may fail to lessen lesion size owing to complications, such as elevated blood pressure, whereas much-delayed hypothermia is beneficial after ICH. Future experiments should assess whether counteracting the side effects of early hypothermia enhances protection.

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