Neural Stem Cell Transplantation Is Associated with Inhibition of Apoptosis, Bcl-xL Upregulation, and Recovery of Neurological Function in a Rat Model of Traumatic Brain Injury.

Traumatic brain injury (TBI) is a common disease that usually causes severe neurological damage, and current treatment is far from satisfactory. The neuroprotective effects of neural stem cell (NSC) transplantation in the injured nervous system have largely been known, but the underlying mechanisms remain unclear, and their limited sources impede their clinical application. Here, we established a rat model of TBI by dropping a weight onto the cortical motor area of the brain and explored the effect of engrafted NSCs (passage 3, derived from the hippocampus of embryonic 12- to 14-d green fluorescent protein transgenic mice) on TBI rats. Moreover, RT-PCR and Western blotting were employed to investigate the possible mechanism associated with NSC grafts. We found rats with TBI exhibited a severe motor and equilibrium dysfunction, while NSC transplantation could partly improve the motor function and significantly reduce cell apoptosis and increase B-cell lymphoma-extra large (Bcl-xL) expression at 7 d postoperation. However, other genes including Bax, B-cell lymphoma 2, Fas ligand, and caspase3 did not exhibit significant differences in expression. Moreover, to test whether Bcl-xL could be used as a therapeutic target, herpes simplex virus (HSV) 1 carrying Bcl-xL recombinant was constructed and injected into the pericontusional cortices. Bcl-xL overexpression not only resulted in a significant improvement in neurological function but also inhibits cell apoptosis, as compared with the TBI rats, and exhibits the same effects as the administration of NSC. The present study therefore indicated that NSC transplantation could promote the recovery of TBI rats in a manner similar to that of Bcl-xL overexpression. Therefore, Bcl-xL overexpression, to some extent, could be considered as a useful strategy to replace NSC grafting in the treatment of TBI in future clinical practices.

Roles of BDNF in spinal neuroplasticity in cats subjected to partial dorsal ganglionectomy.

This study investigated the role of brain-derived neurotrophic factor (BDNF) in neuroplasticity in cats subjected to the removal of dorsal root ganglia (DRG). Following partial ganglionectomy, the number of BDNF-positive varicosities from spared L6 DRG decreased significantly. This reduction was observed at 3 days post operation (dpo) in spinal lamina II of L3 and L5. Whereas the percentages of positive neurons for BDNF and its mRNA in spared L6 DRG at 10 dpo were significantly increased, and accumulated BDNF was seen on the DRG side of the ligated axons. Importantly, BDNF antibody neutralization in vivo results in a significant reduction in the number of varicosities in spinal lamina II, evidenced by BDNF and calcitonin gene-related peptide immunohistochemical staining. These findings suggested that peripheral-derived BDNF could play a critical role in spinal neuroplasticity in cats subjected to partial ganglionectomy. This may underlie the basis of molecular therapy depending on gene drug-like BDNF release.

[Study on the change of angiotensin II expression in rat lung exposure to acrolein].

OBJECTIVE: To investigate the changes of angiotensin II (Ang II) expression in a rat model of mucus hypersecretion induced by acrolein. METHODS: A rat model of mucous hypersecretion of airway was established by acrolein-inhalation. The AB/PAS stain was performed to evaluate the mucous secretion level. Immunohistochemistry and Western blot were employed to detect the expression of Ang II protein. RESULTS: Hypersecretion of mucus occurred at 3 weeks and peaked at 6 weeks post exposure (wpe) to acrolein. Increased immunostaining and protein level of Ang II were readily detected in rat lung at 3 wpe and enhanced at 6 wpe. CONCLUSION: The increase of Ang II expression, which associated to pulmonary mucus hypersecretion, might play a role in the lung injury induced by acrolein exposure.

[Effects of acrolein exposure on the expression of Muc5ac in the airway of rats].

OBJECTIVE: To explore the changes of Muc5ac expression in a rat model of mucus hypersecretion induced by acrolein. METHODS: The rat model of mucus hypersceretion was established by acrolein exposure. RT-PCR, ISH, immunohistochemistry and Western blot were employed to detect the mRNA and protein levels of Muc5ac in the rats airway. RESULTS: The expression of Muc5ac was detected in trachea and lung at 3 weeks post exposure (wpe) and the expression level was enhanced at 6 wpe. ISH confirmed that Muc5ac was synthesized endogenously. CONCLUSION: The pulmonary mucus hypersecretion is associated to the increase of intrinsic Muc5ac expression in the rat airway exposure to acrolein.

[Effects of enalapril on IL-1beta, IL-6 expression in rat lung exposure to acrolein].

OBJECTIVE: To investigate the effects of enalapril on the expressions of IL-1beta and IL-6 in the lung of rats treated with acrolein inhalation. METHODS: Inflammatory lung injury was induced by acrolein inhalation in rats. The rats were divided into natrium solution (NS) group, acrolein group, enalapril and acroclein (EA) group, enalapril and NS (EN) group. Lungs were harvested from the rats in each group at 1 week, 3 weeks, 6 weeks after the treatment of natrium solution, acrolein inhalation and/or enalapril. The mRNA and protein expressions of IL-1beta and IL-6 in the lung tissues were measured by RT-PCR, in situ hybridization, immunohistochemistry and Western blot. RESULTS: Increased immunostaining, protein level and mRNA expression of IL-1beta and IL-6 were found in rat lung at 3 weeks and reached to the peak at 6 weeks post exposure to acrolein. The administration of enalapril resulted in a significant downregulation of IL-1beta and IL-6 in both protein and gene level, accompany with the decrease of inflammation. CONCLUSION: Enalapril, as a ACE inhibitor, could protect the airway from inflammation injury in acrolein-treated rats via the down-regulation of IL-1beta and IL-6 expression.

Role of Neurotrophin 3 in spinal neuroplasticity in rats subjected to cord transection.

That neuroplasticity occurs in mammalian spinal cord is well known, though the underlying mechanism still awaits elucidation. This study evaluated the role of endogenous Neurotrophin-3 (NT-3) in the spinal neuroplasticity. Following cord transection at the junction between T9 and T10, the hindlimb locomotor functions of rats showed gradual but significant improvement from 7 to 28 days post-operation. Corresponding to this was a significant increase in the level of NT-3 in the cord segments caudal to injury site. Significantly, after NT-3-antibody administration, the spinal transected rats displayed poor hindlimb locomotor functions and a decrease in the number of neurons in spinal laminae VIII-IX. Whether NT-3-antibody was administered, corticospinal tract regeneration and somatosensory evoked potentials could not be detected. Our findings suggested that endogenous NT-3 could play an important role in spinal plasticity in adult spinal cords subjected to transection, possibly through a regulation of neuronal activity in the local circuitry.