Spinal root avulsion:an excellent model for studying motoneuron degeneration and regeneration after severe axonal injury

Spinal root avulsion is an excellent model for studying the re- sponse of motoneurons to severe injury to their axons （Koliat- sos et al., 1994）. In this model （‘Avulsion Model＇）, spinal roots are torn off from spinal cord without removing the vertebra at different levels of spinal segments, usually at cervical and lum- bar segments. Step-by-step procedures are described in detail elsewhere （Chu and Wu, 2009）. The Avulsion Model resembles very well brachial plexus injuries in human beings. Around 70% of severe brachial plexus injuries in human involved avulsion of one or more roots （Narakas, 1985） and the main causes of traumatic brachial plexus injuries were motor vehicle accidents, sport injuries and difficult deliveries （Terzis et al., 2001）. The Avulsion Model involves injury to both central nervous system （CNS） and peripheral nervous system （PNS） while nerve axoto- my, transection and crush injuries only involve PNIS.

Improved C_(3-4) transfer for treatment of root avulsion of the brachial plexus upper trunk Animal experiments and clinical application

Experimental rats with root avulsion of the brachial plexus upper trunk were treated with the improved C34 transfer for neurotization of 05-6. Results showed that Terzis grooming test scores were significantly increased at 6 months after treatment, the latency of C5-6 motor evoked potential was gradually shortened, and the amplitude was gradually increased. The rate of C3 instead of C5 and the C4 ＋ phrenic nerve instead of C6 myelinated nerve fibers crossing through the anastomotic stoma was approximately 80%. Myelinated nerve fibers were arranged loosely but the thickness of the myelin sheath was similar to that of the healthy side. In clinical applications, 39 patients with root avulsion of the brachial plexus upper trunk were followed for 6 months to 4.5 years after treatment using the improved C3 instead of C5 nerve root transfer and C4 nerve root and phrenic nerve instead of C6 nerve root transfer. Results showed that the strength of the brachial biceps and deltoid muscles recovered to level IIHV, scapular muscle to level Ill-W, latissimus dorsi and pectoralis major muscles to above level Ⅲ, and the brachial triceps muscle to level 0 Ill. Results showed that the improved 03-4 transfer for root avulsion of the brachial plexus upper trunk in animal models is similar to clinical findings and that C3-4 and the phrenic nerve transfer for neurotization of C5-6 can innervate the avulsed brachial plexus upper trunk and promote the recovery of nerve function in the upper extremity.

Differentiation of endogenous neural stem cells in adult versus neonatal rats after brachial plexus root avulsion injury

An experimental model of brachial plexus root avulsion injury of cervical dorsal C5-6 was established in adult and neonatal rats.Real-time PCR showed that the levels of brain-derived neurotrophic factor,nerve growth factor and neurotrophin-3 in adult rats increased rapidly 1 day after brachial plexus root avulsion injury,and then gradually decreased to normal levels by 21 days.In neonatal rats,levels of the three neurotrophic factors were decreased on the first day after injury,and then gradually increased from the seventh day and remained at high levels for an extended period of time.We observed that greater neural plasticity contributed to better functional recovery in neonatal rats after brachial plexus root avulsion injury compared with adult rats.Moreover, immunohistochemical staining showed that the number of bromodeoxyuridine/nestin-positive cells increased significantly in the spinal cords of the adult rats compared with neonatal rats after brachial plexus root avulsion injury.In addition,the number of bromodeoxyuridine/glial fibrillary acidic protein-positive cells in adult rats was significantly higher than in neonatal rats 14 and 35 days after brachial plexus injury.Bromodeoxyuridine/β-tubulin-positive cells were not found in either adult or neonatal rats.These results indicate that neural stem cells differentiate mainly into astrocytes after brachial plexus root avulsion injury.Furthermore,the degree of neural stem cell differentiation in neonatal rats was lower than in adult rats.

Preconditioning crush increases the survival rate of motor neurons after spinal root avulsion

In a previous study, heat shock protein 27 was persistently upregulated in ventral motor neurons following nerve root avulsion or crush. Here, we examined whether the upregulation of heat shock protein 27 would increase the survival rate of motor neurons. Rats were divided into two groups： an avulsion-only group （avtflsion of the L4 lumbar nerve root only） and a crush-avulsion group （the L4 lumbar nerve root was crushed 1 week prior to the avulsion）. Immunofluores- cent staining revealed that the survival rate of motor neurons was significantly greater in the crush-avulsion group than in the avulsion-only group, and this difference remained for at least 5 weeks after avulsion. The higher neuronal survival rate may be explained by the upregulation of heat shock protein 27 expression in motor neurons in the crush-avulsion group. Further- more, preconditioning crush greatly attenuated the expression of nitric oxide synthase in the motor neurons. Our findings indicate that the neuroprotective action of preconditioning crush is mediated through the upregulation of heat shock protein 27 expression and the attenuation of neuronal nitric oxide synthase upregulation following avulsion.

Functional reconstruction following brachial plexus root avulsion

OBJECTIVE： To sum up the treatment of brachial plexus root avulsion and the progress in functional reconstruction and rehabilitation following brachial plexus root avulsion. DATA SOURCES： A search of Medline was performed to select functional reconstruction and rehabilitation following brachial plexus injury-related English articles published between January 1990 and July 2006, with key words of ＂brachial plexus injury, reconstruction and rehabilitation＂. Meanwhile, a computer-based search of CBM was carried out to select the similar Chinese articles published between January 1998 and July 2006, with key words of ＂brachial plexus injury, reconstruction and rehabilitation＂. STUDY SELECTION： The materials were checked primarily, and the literatures of functional reconstruction and rehabilitation of brachial plexus injury were selected and the full texts were retrieved. Inclusive criteria： ①Functional reconstruction following brachial plexus injury. ②Rehabilitation method of brachial plexus injury. Exclusive criteria： Reviews, repetitive study, and Meta analytical papers. DATA EXTRACTION： Forty-six literatures about functional reconstruction following brachial plexus injury were collected, and 36 of them met the inclusive criteria. DATA SYNTHESIS： Brachial plexus injury causes the complete or incomplete palsy of muscle of upper extremity. The treatment of brachial plexus is to displace not very important nerves to the distal end of very important nerve, called nerve transfer, which is an important method to treat brachial plexus injury. Postoperative rehabilitations consist of sensory training and motor functional training. It is very important to keep the initiativeness of exercise. Besides recovering peripheral nerve continuity by operation, combined treatment and accelerating neural regeneration, active motors of cerebral cortex is also the important factor to reconstruct peripheral nerve function. CONCLUSION： Consciously and actively strengthening functional exercise after operation is helpful to form cerebral plasticity and produce voluntary movements, can re-educate re-dominated muscle, obviously improves postoperative therapeutic effect and promote functional reconstruction.

Sensory regeneration in dorsal root avulsion

Brachial as well as lumbosacral plexus avulsion injuries are usually caused by high kinetic traumas,such as car-pedestrian,car and motorcycle accidents or falls from great heights.Traction forces affecting the head and shoulders or extremities pull the spinal nerve sleeves away from the spinal cord and rupture the postganglionic spinal root from the cord.In so called central avulsion injuries,the spinal root is avulsed at the peripheral nervous system （CNS interface between the central and and PNS）. This results not only in the disconnection of the root from the cord but also in a longitudi- nal spinal cord injury. The complexity of the injury leads to degen- eration of the spinal root and a marked inflammatory response of the spinal cord followed by the formation of a glial scar （Kachra- manoglou et al., 2011）.

Valproic acid protects neurons and promotes neuronal regeneration after brachial plexus avulsion

Valproic acid has been shown to exert neuroprotective effects and promote neurite outgrowth in several peripheral nerve injury models. However, whether valproic acid can exert its beneficial effect on neurons after brachial plexus avulsion injury is currently unknown. In this study, brachial plexus root avulsion models, established in Wistar rats, were administered daily with valproic acid dis-solved in drinking water （300 mg/kg） or normal water. On days 1, 2, 3, 7, 14 and 28 after avulsion injury, tissues of the C 5-T 1 spinal cord segments of the avulsion injured side were harvested to in-vestigate the expression of Bcl-2, c-Jun and growth associated protein 43 by real-time PCR and western blot assay. Results showed that valproic acid significantly increased the expression of Bcl-2 and growth associated protein 43, and reduced the c-Jun expression after brachial plexus avulsion. Our findings indicate that valproic acid can protect neurons in the spinal cord and enhance neuronal regeneration fol owing brachial plexus root avulsion.

Surgical reconstruction of spinal cord circuit provides functional return in humans

This mini review describes the current surgical strategy for restoring function after traumatic spinal nerve root avulsion in brachial or lumbosacral plexus injury in man. As this lesion is a spinal cord or central nervous injury functional return depends on spinal cord nerve cell growth within the central nervous system. Basic science, clinical research and human application has demonstrated good and useful motor function after ventral root avulsion followed by spinal cord reimplantation. Recently, sensory return could be demonstrated following spinal cord surgery bypassing the injured primary sensory neuron. Experimental data showed that most of the recovery depended on new growth reinnervating peripheral receptors. Restored sensory function and the return of spinal reflex was demonstrated by electrophysiology and functional magnetic resonance imaging of human cortex. This spinal cord surgery is a unique treatment of central nervous system injury resulting in useful functional return. Further improvements will not depend on surgical improvements. Adjuvant therapy aiming at ameliorating the activity in retinoic acid elements in dorsal root ganglion neurons could be a new therapeutic avenue in restoring spinal cord circuits after nerve root avulsion injury.

Use of intercostal nerves for different target neurotization in brachial plexus reconstruction

Intercostal nerve transfer is a valuable procedure in devastating plexopathies. Intercostal nerves are a very good choice for elbow flexion or extension and shoulder abduction when the intraplexus donor nerves are not available. The best results are obtained in obstetric brachial plexus palsy patients, when direct nerve transfer is performed within six months from the injury. Unlike the adult posttraumatic patients after median and ulnar nerve neurotization with intercostal nerves, almost all obstetric brachial plexus palsy patients achieve protective sensation in the hand and some of them achieve active wrist and finger flexion. Use in combination with proper muscles, intercostal nerve transfer can yield adequate power to the paretic upper limb. Reinnervation of native muscles(i.e., latissimus dorsi) should always be sought as they can successfully be transferred later on for further functional restoration.