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From a case study, we describe the impact of unilateral lesion of the hand area in the primary motor cortex (M1) on manual dexterity and the role of the intact contralesional M1 in long-term functional recovery. An adult macaque monkey performed two manual dexterity tasks: (i) "modified Brinkman board" task, assessed simple precision grip versus complex precision grip, the latter involved a hand postural adjustment; (ii) "modified Klüver board" task, assessed movements ranging from power grip to precision grip, pre-shaping and grasping. Two consecutive unilateral M1 lesions targeted the hand area of each hemisphere, the second lesion was performed after stable, though incomplete, functional recovery from the primary lesion. Following each lesion, the manual dexterity of the contralesional hand was affected in a comparable manner, effects being progressively more deleterious from power grip to simple and then complex precision grips. Both tasks yielded consistent data, namely that the secondary M1 lesion did not have a significant impact on the recovered performance from the primary M1 lesion, which took place 5months earlier. In conclusion, the intact contralesional M1 did not play a major role in the long-term functional recovery from a primary M1 lesion targeted to the hand area., (Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.)

With the ever increasing incidence of brain injury, developing new tissue engineering strategies to promote neural tissue regeneration is an enormous challenge. The goal of this study was to design and evaluate an implantable scaffold capable of directing neurite and axonal growth for neuronal brain tissue regeneration. We have previously shown in cell culture conditions that engineered micropatterned PDMS surface with straight microchannels allow directed neurite growth without perturbing cell differentiation and neurite outgrowth. In this study, the micropatterned PDMS device pre-seeded with hNT2 neuronal cells were implanted in rat model of primary motor cortex lesion which induced a strong motor deficit. Functional recovery was assessed by the forelimb grip strength test during 3 months post implantation. Results show a more rapid and efficient motor recovery with the hNT2 neuroimplants associated with an increase of neuronal tissue reconstruction and cell survival. This improvement is also hastened when compared to a direct cell graft of ten times more cells. Histological analyses showed that the implant remained structurally intact and we did not see any evidence of inflammatory reaction. In conclusion, PDMS bioimplants with guided neuronal cells seem to be a promising approach for supporting neural tissue reconstruction after central brain injury., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Rats were given bilateral lesions of the motor cortex on the tenth day of life, and then received a daily subcutaneously injection of either basic fibroblast growth factor (FGF-2) or vehicle for 7 consecutive days. In adulthood, they were trained and assessed on a skilled forelimb reaching task. Although all lesion groups were impaired at skilled reaching, the postnatal day 10-lesioned group that received FGF-2 was less impaired than the lesion group that received the vehicle. Furthermore, the lesioned rats that received FGF-2 showed a filling of the lesion cavity with tissue, whereas the lesioned vehicle-treated rats still had a prominent lesion cavity. The functionality of the tissue filling the cavity, tissue surrounding it, and tissue from the motor cortex (in control rats) was assessed using intracortical microstimulation, and showed that stimulation of some sites from the filled cavity could evoke movement. The rats were perfused and processed for Golgi-Cox staining. Medium spiny neurons from the striatum were drawn and analyzed, and the results suggest that postnatal day 10 lesions of the motor cortex induced an increase in the length and complexity of these cells compared with those of non-lesioned rats. Our results suggest that FGF-2 may play an important role in recovery from early brain damage.

Previous studies have utilized a lesion model of cortical injury that produces transient behavioral impairments to investigate the recovery of function process. To better understand the recovery process, it would be beneficial to use a lesion model that produces more severe, enduring, behavioral impairments. The purpose of experiment 1 was to validate whether large lesions of the sensorimotor cortex (SMC), which included the rostral forelimb and caudal forelimb regions, produced enduring behavioral deficits. Rats were given large unilateral electrolytic lesions of the SMC, administered either the N-methyl-D-aspartate (NMDA) antagonist, MK-801 or saline 16 h after injury, and tested on a battery of behavioral tests. Enduring behavioral deficits were observed, for at least 6 months, on two tests of forelimb placing while transient deficits were observed on the foot-fault and somatosensory neutralization tests. Administration of MK-801 facilitated recovery on the somatosensory neutralization test; however, it did not induce recovery on either forelimb placing test. A second experiment was performed to determine if earlier administration of MK-801, the NMDA antagonist magnesium chloride (MgCl(2)), or the anti-oxidant N-tert-butyl-alpha-phenylnitrone (PBN) could induce behavioral recovery in this chronic model. Treatment with these drugs induced behavioral recovery on the forelimb placing tests, whereas, the saline-treated rats did not show any signs of behavioral recovery for at least 3 months. Anatomical analysis of the striatum showed that MK-801 and MgCl(2) but not PBN reduced the extent of lesion-induced striatal atrophy. These results suggest that administration of MK-801, MgCl(2), or PBN shortly after cortical injury can induce recovery of function when recovery is otherwise not expected in un-treated rats.

Motor recovery after unilateral sensorimotor cortex ablation or sham-injury was measured in apolipoprotein E knockout and wild-type mice by testing their abilities to traverse a narrow beam. All mice trained without difficulty. Sham-operated mice performed perfectly regardless of genotype throughout testing. There was no difference in motor scores between lesioned apolipoprotein E knockout and wild-type mice on a first trial 24h after injury (P>0.05). There was a significant overall effect of lesion on motor performance (two-way repeated measures analysis of variance F(1,42)=304, P<0.0001), a significant time effect (F(17,714)=58, P<0.0001) and a lesion by time interaction (F(17,714)=58, P<0.0001). However, there was no effect of apolipoprotein E genotype group on recovery rate (i.e. there was no lesion group by genotype group by time interaction, F(17,714)=0.33, P=1.00) and no effect of genotype on the final level of motor performance 12 days after the lesion (Kruskal-Wallis H=5.79, P=0.12). These data suggest that motor recovery after unilateral injury to the sensorimotor cortex does not vary with apolipoprotein E genotype.

Although it has been shown that unilateral neonatal cortical ablation induces bilateral corticospinal projections, the explanation for the pathways responsible for this bilateral innervation remains controversial. We hypothesized that such reinnervation may be supplied from newly formed fibers sprouting at the level rostral to, or at, or caudal to the pyramidal decussation. In order to test our hypothesis, we examined the brain and spinal cord of young hamsters which had a unilateral ablation of the right motor cortex at six days postnatally, and then received an injection of an anterograde neuronal lectin tracer, Phaseolus vulgaris-leucoagglutinin, into the hindlimb area of the left motor cortex at 21 days postnatally. For the identification of motoneurons in the lumbar spinal cord, some of these animals also received an injection of cholera toxin subunit B, a retrograde tracer, into the gastrocnemius muscle. A quantitative analysis in the left gray matter of the lumbar spinal cord indicated that the lectin labeling was two to eight times higher in cortically ablated animals than in intact animals. Immunohistochemical detection of the lectin revealed that innervation of the left spinal cord occurred close to targets at lower levels in the spinal cord. Two modes of reinnervation (types I and II) by the intact corticospinal tract were recognized. The type I fibers consisted of recrossing axon collaterals sprouted from the intact dorsal funiculus near their targets, while the type II fibers were recrossing parent axons which entered the intact, right gray matter several levels rostral to their targets, and then changed direction toward the targets. The recrossing at lower spinal levels yielded a large number of ipsilaterally labeled axons and their terminals in the gray matter of the denervated lumbar cord, with a distribution pattern similar to that seen on the intact side. The present results indicate that such ipsilateral innervation may play an important role in the sparing and recovery of function following neonatal hemicortical injury.

Functional recovery after brain damage has been described frequently and different mechanisms have been proposed to account for the observed recovery. One possible mechanism involves the capacity of one part of the brain to take over the function of another. A possible area for this to take place is in the cerebral cortex, where a variety of reorganizational processes have been described after different manipulations. We show in the present study that the forelimb force and response capacity of the rat, which becomes highly impaired after the bilateral ablation of the forelimb primary motor cortex, is recovered when the animals receive an electrical stimulation in the ventral tegmental nucleus contingent to each forelimb response in the task. Microstimulation mapping of the cortical areas adjacent to the forelimb primary motor cortex revealed the appearance of an area located caudolaterally to the forelimb primary motor cortex, where forelimb movements could be evoked in recovered animals but to a lesser extent in non-recovered animals. A positive and significant correlation was observed between the size of the reorganized forelimb area and the behavioral performance of the animals. Ablation of the forelimb reorganized area in recovered animals reinstated the forelimb behavioral impairment, while the same lesion in normal animals had no effect on the behavioral performance. The results indicate that recovery after bilateral forelimb primary motor cortex ablation may be due to the organization of specific adjacent areas in the cortex.

This study reports the effects of norepinephrine infusions into cerebellum after unilateral sensorimotor cortex injury. The results demonstrate an immediate and permanent acceleration in motor recovery in awake rats infused with 150 micrograms norepinephrine into the cerebellum contralateral to a right sensorimotor cortex ablation. A vehicle infusion or infusion of norepinephrine into the ipsilateral cerebellum produced no beneficial effects on functional recovery.