Effects of bone marrow mononuclear cells on induction of axonal sprouting in cortico-cortical and cortico-striatal pathways in an animal model of cortical ablation.

Objectives Many therapies have been proposed in order to investigate the mechanisms of neural repair associated with neurological diseases, including BMMC (Bone marrow Mononuclear Cells) transplantation. However, studies show that some brain injuries are less responsive to neural repair, such as, for example, cortical ablation. On the other hand, models of cortical ablation have shown functional recovery after BMMC transplantation. Thus, it is relevant to expand knowledge about BMMC, also, in the induction of neuroplasticity, in this model, considering treating a promising event for the rehabilitation of neurological diseases. Using the experimental model of cortical ablation, adult male Wistar rats, which is known to be poorly responsive to neuroplasticity, the aim of this study was to investigate the effects of BMMC on axonal sprouting induction in cortico-cortical and cortico-striatal projections. An anterograde neurotracer was used to evaluate the distribution of axonal fibers.ResultsQuantitative analyses were performed and the results showed that BMMC were not able to significantly induce axonal sprouting in the evaluated areas. Our results reinforced the idea that cortical ablation may be less responsive to neuroplasticity and the beneficial effects of BMMC therapy depend on the particularities of a neural microenvironment intrinsic to a given lesion.

Effects of bone marrow mononuclear cells on induction of axonal sprouting in cortico-cortical and cortico-striatal pathways in an animal model of cortical ablation.

Many therapies have been proposed in order to investigate the mechanisms of neural repair associated with neurological diseases, including BMMC (bone marrow mononuclear cells) transplantation. However, studies show that some brain injuries are less responsive to neural repair, such as, for example, cortical ablation. On the other hand, models of cortical ablation have shown functional recovery after BMMC transplantation. Thus, it is relevant to expand knowledge about BMMC, also, in the induction of neuroplasticity, in this model, considering treating a promising event for the rehabilitation of neurological diseases. Using the experimental model of cortical ablation of the sensorimotor cortex, which is known to be poorly responsive to neuroplasticity, the aim of this study was to investigate the effects of BMMC on axonal sprouting induction in cortico-cortical and cortico-striatal projections. An anterograde neurotracer was used to evaluate the distribution of axonal fibers. Quantitative analyzes were performed and the results showed that BMMC were not able to significantly induce axonal sprouting in the evaluated areas. Our results reinforced the idea that cortical ablation may be less responsive to neuplasticity and the beneficial effects of BMMC therapy depend on the particularities of a neural microenvironment intrinsic to a given lesion.

Factors Involved in the Functional Motor Recovery of Rats with Cortical Ablation after GH and Rehabilitation Treatment: Cortical Cell Proliferation and Nestin and Actin Expression in the Striatum and Thalamus

Previously we demonstrated, in rats, that treatment with growth hormone (GH) and rehabilitation, carried out immediately after a motor cortical ablation, significantly improved the motor affectation produced by the lesion and induced the re-expression of nestin in the contralateral motor cortex. Here we analyze cortical proliferation after ablation of the frontal motor cortex and investigate the re-expression of nestin in the contralateral motor cortex and the role of the striatum and thalamus in motor recovery. The rats were subjected to ablation of the frontal motor cortex in the dominant hemisphere or sham-operated and immediately treated with GH or the vehicle (V), for five days. At 1 dpi (days post-injury), all rats received daily injections (for four days) of bromodeoxyuridine and five rats were sacrificed at 5 dpi. The other 15 rats (n = 5/group) underwent rehabilitation and were sacrificed at 25 dpi. GH induced the greatest number of proliferating cells in the perilesional cortex. GH and rehabilitation produced the functional recovery of the motor lesion and increased the expression of nestin in the striatum. In the thalamic ventral nucleus ipsilateral to the lesion, cells positive for nestin and actin were detected, but this was independent on GH. Our data suggest that GH-induced striatal nestin is involved in motor recovery.

Factors Involved in the Functional Motor Recovery of Rats with Cortical Ablation after GH and Rehabilitation Treatment: Cortical Cell Proliferation and Nestin and Actin Expressions in Striatum and Thalamus

Previously we demonstrated, in rats, that the treatment with growth hormone (GH) and rehabilitation, carried out immediately after a motor cortical ablation, significantly improved the motor affectation produced by the lesion and induced the re-expression of nestin in the contralateral motor cortex. Here we analyze cortical proliferation after ablation of the frontal motor cortex and investigate the re-expression of nestin in the contralateral motor cortex and the role of the striatum and thalamus in motor recovery. The rats were subjected to ablation of the frontal motor cortex in the dominant hemisphere or sham-operated and immediately treated with GH or vehicle (V), for five days. At 1 dpi (days after injury), 5 rats received daily injections (4 days) of bromodeoxyuridine and were sacrificed. The other 15 rats (n = 5 / group) underwent treatment and rehabilitation and were sacrificed at 25 dpi. GH induced the greatest number of proliferating cells in the perilesional cortex. GH and rehabilitation produced the functional recovery of the motor lesion and increased the expression of nestin in the striatum. In the thalamic ventral nucleus ipsilateral to the lesion, cells positive for nestin and actin were detected, but this was independent of GH. Our data suggest that GH-induced striatal nestin is involved in motor recovery.

Motor Improvement of Skilled Forelimb Use Induced by Treatment with Growth Hormone and Rehabilitation Is Dependent on the Onset of the Treatment after Cortical Ablation

We previously demonstrated that the administration of GH immediately after severe motor cortex injury, in rats, followed by rehabilitation, improved the functionality of the affected limb and reexpressed nestin in the contralateral motor cortex. Here, we analyze whether these GH effects depend on a time window after the injury and on the reexpression of nestin and actin. Injured animals were treated with GH (0.15 mg/kg/day) or vehicle, at days 7, 14, and 35 after cortical ablation. Rehabilitation was applied at short and long term (LTR) after the lesion and then sacrificed. Nestin and actin were analyzed by immunoblotting in the contralateral motor cortex. Giving GH at days 7 or 35 after the lesion, but not 14 days after it, led to a remarkable improvement in the functionality of the affected paw. Contralateral nestin and actin reexpression was clearly higher in GH-treated animals, probably because compensatory brain plasticity was established. GH and immediate rehabilitation are key for repairing brain injuries, with the exception of a critical time period: GH treatment starting 14 days after the lesion. Our data also indicate that there is not a clear plateau in the recovery from a brain injury in agreement with our data in human patients.

Topectomy versus leukotomy: J. Lawrence Pool’s contribution to psychosurgery

Surgery of the mind has a rather checkered past. Though its history begins with the prehistoric trephination of skulls to allow “evil spirits” to escape, the early- to mid-20th century saw a surge in the popularity of psychosurgery. The 2 prevailing operations were topectomy and leukotomy for the treatment of certain mental illnesses. Although they were modified and refined by several of their main practitioners, the effectiveness of and the ethics involved with these operations remained controversial.In 1947, Dr. J. Lawrence Pool and the Columbia-Greystone Associates sought to rigorously investigate the outcomes of specific psychosurgical procedures. Pool along with R. G. Heath and John Weber believed that nonexcessive bifrontal cortical ablation could successfully treat certain mental illnesses without the undesired consequences of irreversible personality changes. They conducted this investigation at the psychiatric hospital at Greystone Park near Morristown, New Jersey.Despite several encouraging findings of the Columbia-Greystone project, psychosurgery practices began to decline significantly in the 1950s. The uncertainty of results and ethical debates related to side effects made these procedures unpopular. Further, groups such as the National Association for the Advancement of Colored People and the American Civil Liberties Union condemned the use of psychosurgery, believing it to be an inhumane form of treatment. Today, there are strict guidelines that must be adhered to when evaluating a patient for psychosurgery procedures. It is imperative for the neurosurgery community to remember the history of psychosurgery to provide the best possible current treatment and to search for better future treatments for a particularly vulnerable patient population.