Outcomes and prognostic factors for nerve grafting following high radial nerve injury.

In this study, we examined the prognostic factors affecting outcomes following nerve grafting in high radial nerve injuries. Thirty-three patients with radial nerve injuries at a level distal to the first branch to the triceps and proximal to the posterior interosseous nerve were retrospectively studied. After a follow-up of at least 1 year, 24 patients (73%) obtained M3+ wrist extension, 16 (48%) obtained M3+ finger extension and only ten (30%) obtained M3+ thumb extension. Univariate, multivariate and receiver operating characteristic analyses showed that a delay in the repair of less than 6 months, a defect length of less than 5 cm or when grafted with three or more donor nerve cables achieved better recovery. Number of cables used was related to muscle strength recovery but not time to reinnervation. Nerve grafting for high radial nerve injury achieved relatively good wrist extension but poor thumb extension and is affected by certain prognostic factors. Level of evidence: IV.

Restoring After Central Nervous System Injuries: Neural Mechanisms and Translational Applications of Motor Recovery.

Central nervous system (CNS) injuries, including stroke, traumatic brain injury, and spinal cord injury, are leading causes of long-term disability. It is estimated that more than half of the survivors of severe unilateral injury are unable to use the denervated limb. Previous studies have focused on neuroprotective interventions in the affected hemisphere to limit brain lesions and neurorepair measures to promote recovery. However, the ability to increase plasticity in the injured brain is restricted and difficult to improve. Therefore, over several decades, researchers have been prompted to enhance the compensation by the unaffected hemisphere. Animal experiments have revealed that regrowth of ipsilateral descending fibers from the unaffected hemisphere to denervated motor neurons plays a significant role in the restoration of motor function. In addition, several clinical treatments have been designed to restore ipsilateral motor control, including brain stimulation, nerve transfer surgery, and brain-computer interface systems. Here, we comprehensively review the neural mechanisms as well as translational applications of ipsilateral motor control upon rehabilitation after CNS injuries.

Crossing nerve transfer drives sensory input-dependent plasticity for motor recovery after brain injury.

Restoring limb movements after central nervous system injury remains a substantial challenge. Recent studies proved that crossing nerve transfer surgery could rebuild physiological connectivity between the contralesional cortex and the paralyzed arm to compensate for the lost function after brain injury. However, the neural mechanism by which this surgery mediates motor recovery remains still unclear. Here, using a clinical mouse model, we showed that this surgery can restore skilled forelimb function in adult mice with unilateral cortical lesion by inducing cortical remapping and promoting corticospinal tract sprouting. After reestablishing the ipsilateral descending pathway, resecting of the artificially rebuilt peripheral nerve did not affect motor improvements. Furthermore, retaining the sensory afferent, but not the motor efferent, of the transferred nerve was sufficient for inducing brain remapping and facilitating motor restoration. Thus, our results demonstrate that surgically rebuilt sensory input triggers neural plasticity for accelerating motor recovery, which provides an approach for treating central nervous system injuries.

A Mouse Model of Direct Anastomosis via the Prespinal Route for Crossing Nerve Transfer Surgery.

Crossing nerve transfer surgery has been a powerful approach for repairing injured upper extremities in patients with brachial plexus avulsion injuries. Recently, this surgery was creatively applied in the clinical treatment of brain injury and achieved substantial rehabilitation of the paralyzed arm. This functional recovery after the surgery suggests that peripheral sensorimotor intervention induces profound neuroplasticity to compensate for the loss of function after brain damage; however, the underlying neural mechanism is poorly understood. Therefore, an emergent clinical animal model is required. Here, we simulated clinical surgery to establish a protocol of direct anastomosis of bilateral brachial plexus nerves via the prespinal route in mice. Neuroanatomical, electrophysiological, and behavioral experiments helped identify that the transferred nerves of these mice successfully reinnervated the impaired forelimb and contributed to accelerating motor recovery after brain injury. Therefore, the mouse model revealed the neural mechanisms underlying rehabilitation upon crossing nerve transfer after central and peripheral nervous system injuries.

A novel mouse model of contralateral C7 transfer via the pretracheal route: A feasibility study.

BACKGROUND: Contralateral seventh cervical nerve transfer (contralateral C7 transfer) is a novel treatment for patients with spastic paralysis, including stroke and traumatic brain injury. However, little is known on changes in plasticity that occur in the intact hemisphere after C7 transfer. An appropriate surgical model is required. NEW METHOD: We described in detail the anatomy of the C7 in a mouse model. We designed a pretracheal route by excising the contralateral C6 lamina ventralis, and the largest nerve defect necessary for direct neurorrhaphy was compared with defect lengths in a prespinal route. To test feasibility, we performed in-vivo surgery and assessed nerve regeneration by immunofluorescence, histology, electrophysiology, and behavioral examinations. RESULTS: Two types of branching were found in the anterior and posterior divisions of C7, both of which were significantly larger than the sural nerve. The length of the nerve defect was drastically reduced after contralateral C6 lamina ventralis excision. Direct tension-free neurorrhaphy was achieved in 66.7% of mice. The expression of neurofilament in the distal segment of the regenerated C7 increased. Histological examination revealed remyelination. Behavioral tests and electrophysiology tests showed functional recovery in a traumatic brain injury mouse. COMPARISON WITH EXISTING METHODS: This is the first direct tension-free neurorrhaphy mouse model of contralateral C7 transfer which shortened the time of nerve regeneration; previous models have used nerve grafting. CONCLUSIONS: This paper describes a simple, reproducible, and effective mouse model of contralateral C7 transfer for studying brain plasticity and exploring potential new therapies after unilateral cerebral injury.

Tac1-Expressing Neurons in the Periaqueductal Gray Facilitate the Itch-Scratching Cycle via Descending Regulation.

Uncontrollable itch-scratching cycles lead to serious skin damage in patients with chronic itch. However, the neural mechanism promoting the itch-scratching cycle remains elusive. Here, we report that tachykinin 1 (Tac1)-expressing glutamatergic neurons in the lateral and ventrolateral periaqueductal gray (l/vlPAG) facilitate the itch-scratching cycle. We found that l/vlPAG neurons exhibited scratching-behavior-related neural activity and that itch-evoked scratching behavior was impaired after suppressing the activity of l/vlPAG neurons. Furthermore, we showed that the activity of Tac1-expressing glutamatergic neurons in the l/vlPAG was elevated during itch-induced scratching behavior and that ablating or suppressing the activity of these neurons decreased itch-induced scratching behavior. Importantly, activation of Tac1-expressing neurons induced robust spontaneous scratching and grooming behaviors. The scratching behavior evoked by Tac1-expressing neuron activation was suppressed by ablation of spinal neurons expressing gastrin-releasing peptide receptor (GRPR), the key relay neurons for itch. These results suggest that Tac1-expressing neurons in the l/vlPAG promote itch-scratching cycles.

Deep-brain magnetic stimulation promotes adult hippocampal neurogenesis and alleviates stress-related behaviors in mouse models for neuropsychiatric disorders.

BACKGROUND: Repetitive Transcranial Magnetic Stimulation (rTMS)/ Deep-brain Magnetic Stimulation (DMS) is an effective therapy for various neuropsychiatric disorders including major depression disorder. The molecular and cellular mechanisms underlying the impacts of rTMS/DMS on the brain are not yet fully understood. RESULTS: Here we studied the effects of deep-brain magnetic stimulation to brain on the molecular and cellular level. We examined the adult hippocampal neurogenesis and hippocampal synaptic plasticity of rodent under stress conditions with deep-brain magnetic stimulation treatment. We found that DMS promotes adult hippocampal neurogenesis significantly and facilitates the development of adult new-born neurons. Remarkably, DMS exerts anti-depression effects in the learned helplessness mouse model and rescues hippocampal long-term plasticity impaired by restraint stress in rats. Moreover, DMS alleviates the stress response in a mouse model for Rett syndrome and prolongs the life span of these animals dramatically. CONCLUSIONS: Deep-brain magnetic stimulation greatly facilitates adult hippocampal neurogenesis and maturation, also alleviates depression and stress-related responses in animal models.