Neural regeneration therapy after spinal cord injury induces unique brain functional reorganizations in rhesus monkeys.

PURPOSE: Spinal cord injury (SCI) destroys the sensorimotor pathway and induces brain plasticity. However, the effect of treatment-induced spinal cord tissue regeneration on brain functional reorganization remains unclear. This study was designed to investigate the large-scale functional interactions in the brains of adult female Rhesus monkeys with injured and regenerated thoracic spinal cord. MATERIALS AND METHODS: Resting-state functional magnetic resonance imaging (fMRI) combined with Granger Causality analysis (GCA) and motor behaviour analysis were used to assess the causal interaction between sensorimotor cortices, and calculate the relationship between causal interaction and hindlimb stepping in nine Rhesus monkeys undergoing lesion-induced spontaneous recovery (injured, n = 4) and neurotrophin-3/chitosan transplantation-induced regeneration (NT3-chitosan, n = 5) after SCI. RESULTS: The results showed that the injured and NT3-chitosan-treated animals had distinct spatiotemporal features of brain functional reorganization. The spontaneous recovery followed the model of "early intra-hemispheric reorganization dominant, late inter-hemispheric reorganization dominant", whereas regenerative therapy animals showed the opposite trend. Although the variation degree of information flow intensity was consistent, the tendency and the relationship between local neuronal activity properties and coupling strength were different between the two groups. In addition, the injured and NT3-chitosan-treated animals had similar motor adjustments but various relationship modes between motor performance and information flow intensity. CONCLUSIONS: Our findings show that brain functional reorganization induced by regeneration therapy differed from spontaneous recovery after SCI. The influence of unique changes in brain plasticity on the therapeutic effects of future regeneration therapy strategies should be considered. Key messagesNeural regeneration elicited a unique spatiotemporal mode of brain functional reorganization in the spinal cord injured monkeys, and that regeneration does not simply reverse the process of brain plasticity induced by spinal cord injury (SCI).Independent "properties of local activity - intensity of information flow" relationships between the injured and treated animals indicating that spontaneous recovery and regenerative therapy exerted different effects on the reorganization of the motor network after SCI.A specific information flow from the left thalamus to the right insular can serve as an indicator to reflect a heterogeneous "information flow - motor performance" relationship between injured and treated animals at similar motor adjustments.

NT3-chitosan enables de novo regeneration and functional recovery in monkeys after spinal cord injury.

Spinal cord injury (SCI) often leads to permanent loss of motor, sensory, and autonomic functions. We have previously shown that neurotrophin3 (NT3)-loaded chitosan biodegradable material allowed for prolonged slow release of NT3 for 14 weeks under physiological conditions. Here we report that NT3-loaded chitosan, when inserted into a 1-cm gap of hemisectioned and excised adult rhesus monkey thoracic spinal cord, elicited robust axonal regeneration. Labeling of cortical motor neurons indicated motor axons in the corticospinal tract not only entered the injury site within the biomaterial but also grew across the 1-cm-long lesion area and into the distal spinal cord. Through a combination of magnetic resonance diffusion tensor imaging, functional MRI, electrophysiology, and kinematics-based quantitative walking behavioral analyses, we demonstrated that NT3-chitosan enabled robust neural regeneration accompanied by motor and sensory functional recovery. Given that monkeys and humans share similar genetics and physiology, our method is likely translatable to human SCI repair.

Asleep-awake-asleep regimen for epilepsy surgery: a prospective study of target-controlled infusion versus manually controlled infusion technique.

BACKGROUND: Asleep-awake-asleep (AAA) protocol for epilepsy surgery is a unique opportunity to accurately map epilepsy foci involved in motor and eloquent areas, allowing the operator to optimize the resection. Two different application modes of intravenous anesthesia for AAA craniotomies are widely used: infusion by means of target-controlled infusion (TCI) and traditional manually-controlled infusion (MCI). We conducted this study to examine whether intravenous anesthesia using the TCI system with propofol and remifentanil would be a more effective method than MCI in AAA epilepsy surgery. METHODS: This prospective and single center study compared patients undergoing either TCI or MCI techniques for functional AAA epilepsy surgery. 35 cases used TCI including TCI-E (resection of epileptogenic foci in an eloquent area, n = 18) and TCI-M (resection of epileptogenic foci in a motor area, n = 17). Thirty-six cases used MCI including MCI-E (epileptogenic foci in an eloquent area, n = 16) and MCI-M (epileptogenic foci in a motor area, n = 20). Bispectral index value and hemodynamic profiles at different time points during the awake phase were recorded along with time for awakening and the occurrences of adverse events. RESULTS: The TCI technique significantly shortened intraoperative awakening times during the third phase, TCI-E vs MCI-E 12.82 min ± 6.93 vs 29.9 min ± 9.04 (P = .000) and TCI-M vs MCI-M 16.8 min ± 5.19 vs 30.91 min ± 15.32 (P = .010). During the awake phase, the highest bispectral index score values appeared in the TCI-E group at all-time points. Mean arterial pressure and heart rate were more stable in the TCI-E group compared with the MCI-E group during the awake phase. Tachycardia and hypertension were most common in the MCI-E group (52.9% and 29.4%, P = .001 and P = .064). CONCLUSION: We found the superiority of TCI, which is faster intraoperative awakening and better hemodynamics along with secure airway management conditions. It is suggested that the TCI technique may be a feasible and effective technique and it might be a viable replacement of the MCI technique for AAA epilepsy surgery.

[Application of dexmedetomidine for brain nuclei lesion of patients with Parkinson's disease].

OBJECTIVE: To observe the sedative and analgesic effects of dexmedetomidine (Dex) and its influence on respiration and blood pressure, evaluate electrophysiological monitoring and explore the optimal dose of Dex for brain nuclei lesion in Parkinson's disease (PD) patients. METHODS: Approved by hospital ethics committee, 60 PD patients undergoing brain nuclei lesion ablation were randomly allocated into 3 groups (n = 20 each). No sedative anesthetic was used in group A; In group B, Dex 0.3 µg/kg intravenously for initial bolus (duration 15 min) and then 0.3 µg·kg(-1)·h(-1) continuous infusion; In group C, Dex 0.5 µg/kg intravenously (duration 15 min) for initial load and then 0.3 µg·kg(-1)·h(-1) continuous infusion. The parameters of mean arterial pressure (MAP), heart rate (HR), pressure of end-tidal carbon dioxide (P ETCO2), respiratory rate, blood oxygen saturation (SpO2), observer's assessment of alertness/sedation (OAA/S) and verbal rating score (VRS) were recorded at 0 min (baseline), 5 min (T1), 10 min (T2), 15 min (T3), 20 min (T4), 30 min (T5) and 60 min (T6) after the dosing of Dex. RESULTS: HR and respiratory rate decreased in groups B and C compared with baseline. In group C, P ETCO2 was much higher, compared with baseline (P < 0.05). Blood pressures of three groups were well-controlled. The incidence of pain (VRS ≥ 1) in group A was significantly higher than those of groups B and C (P < 0.05). And the incidence of sedation (OAA/S > 1) in group C was much higher than those of groups A and B. The electrophysiological signal of two patients in group C was severely affected. CONCLUSION: At an initial intravenous dose of Dex 0.3 µg/kg and a maintenance dose of 0.3 µg ·kg(-1)·h(-1), electrophysiological monitoring for surgery is not affected in PD patients undergoing brain nuclei lesion ablation. With a minimal interference of breath, Dex has not only well-controlled effects on sedation, analgesia and blood pressure, but also makes patients comfortable.