Development of a novel experimental rat model for neonatal pre-ganglionic upper brachial plexus injury
Introduction
Upper brachial nerve injuries in neonates present unexpected and potentially catastrophic obstetric emergencies at an incidence of 0.15–0.63% (Nielson and Gonik, 1996). The upper brachial plexus, which is composed of the roots of spinal vertebra C5–C7, is most frequently affected in neonates, resulting in a condition called Erb's palsy. Once the injury occurs, serious neurological deficits, such as weakness, sensory disturbance, and atrophy or dystonia of the shoulder and arm may follow. The pathogenesis of congenital brachial plexus palsy remains unclear. It was first described by Danyau (1851). Previous clinical reports suggest that the possible cause was traction of the brachial nerve by extreme lateral extension of the neck and shoulder during delivery (Allen et al., 1991, Wilbourn, 1993). However, recent reports suggest that some injuries may occur as a result of maladaptation of the fetus in utero (Dunn and Engle, 1985, Jennett et al., 1999, Koenigsberger, 1980). Although newborns recover spontaneously during the first few months in most cases, approximately 20% of those affected have permanent motor deficits. The most severe form of this injury is complete avulsion of the nerve from the cervical column and/or a preganglionic root injury. With these injuries, spontaneous recovery is generally not possible. In such cases, surgical treatments, such as shoulder joint fixation, trapezius muscle transplantation or intercostal nerve transplantation have been performed, but the possibility of recovery remain poor (Allen et al., 1991, Xu et al., 2000).
There have been some experimental models for adult brachial plexus injury (Wu and Li, 1993, Bertelli and Mira, 1994, Bertelli et al., 1994, Wu et al., 1995, Wu, 1996, Zhao et al., 1998, Gonik et al., 1998, Spinner et al., 2000), but the adult models do not apply to neonates because of the differences in clinical presentation and histological changes after an adult injury (Pollin et al., 1991, Gonik et al., 1998). There have been few reports about experimental models for brachial nerve palsy in neonates (Tada et al., 1979, Wu et al., 1995). However, the existing evaluations focused on histological changes in an impaired cervical cord and provided inadequate observations of behavioral abnormalities. In the development of a new experimental model, it would be imperative to conduct a detailed behavioral evaluation as well as a histological evaluation. Furthermore, the rat should be used to establish a brachial plexus injury model because the components and branching pattern of the rat brachial plexus are similar to those of humans (Bertelli et al., 1992).
In this study, in order to establish an experimental animal model for neonate Erb's palsy, especially the severe preganglionic type, we created a preganglionic cervical root transection model using 7-day-old rats and evaluated its suitability as a model for neonate Erb's palsy from a behavioral and histological viewpoint. This model should serve as a research tool in the development of new treatments for Erb's palsy.
Section snippets
Animals and surgical procedure
This study was approved by the Animal Research Committee of Miyazaki Medical College. Pregnant Wistar rats were purchased from Japan Charles River (Shizuoka, Japan). Neonatal Wistar rats were used in this study. They were divided into two groups: those receiving the Erb operation and those receiving a sham operation. Each group was composed of ten rats. All operations were performed on 7-day-old rats under a dissection microscope. Adequate anesthesia was used and maintained by ether inhalation.
Clinical score
As shown in Fig. 3, on the 1st and 2nd week after the operation, all rats receiving the Erb operation had flexion in the forelimb ipsilateral to the sectioned site and walking deficits with trailing of the forelimb (Score 0, 0/5; Score 1, 1/5; Score 2, 4/5; 1st, P<0.01, 2nd, P<0.05 by the Mann–Whitney U-test). The clinical score decreased slightly on the 3rd week after the operation (Score 0, 1/5; Score 1, 3/5; Score 2, 1/5), and the score then remained the same for each period examined (3rd to
Discussion
Erb's palsy presents with specific, characteristic features (Alfonso et al., 2000, Dodds and Wolfe, 2000). The following criteria must be met to establish an animal model for neonate Erb's palsy. Firstly weakness in the shoulder and arm without loss of handgrip. As muscle power in the handgrip is connected to the nerve in the C8 root and this root is not affected in Erb's palsy hand grip remain intact. Consequently any loss or decrease in the number of anterior horn cells on the C5–C7 levels is
References (27)
- et al.
Focal upper extremity neuropathy in neonates
Semin. Pediatr. Neurol.
(2000) - et al.
Behavioral evaluating methods in the objective clinical assessment of motor function after experimental brachial plexus reconstruction in the rat
J. Neurosci. Methods
(1993) - et al.
Median nerve neurotization by peripheral nerve grafts directly implanted into the spinal cord: anatomical, behavioural and electrophysiological evidence of sensorimotor recovery
Brain Res.
(1994) - et al.
Brachial plexus palsy: intrauterine onest
Pediatr. Neurol.
(1985) - et al.
The timing of congenital brachial plexus injury: a study of electromyography findings in the newborn piglet
Am. J. Obstet. Gynecol.
(1998) - et al.
Experimental study of spinal nerve repair after plexus brachialis injury in newborn rats: a horseradish peroxidase study
Exp. Neurol.
(1979) Potential roles of gene expression change in adult rat spinal motoneurons following axonal injury: a comparison among c-jun, low affinity nerve growth factor receptor (LNGFR), and nitric oxide synthase (NOS)
Exp. Neurol.
(1996)- et al.
Inhibition of nitric oxide synthase reduces motoneuron death due to spinal root avulsion
Neurosci. Lett.
(1993) - et al.
Induction of nitric oxide synthase and motoneuron death in newborn and early postnatal rats following spinal root avulsion
Neurosci. Lett.
(1995) - et al.
Risk factors for shoulder dystonica: an engineering study of clinician-applied forces
Obstet. Gynecol.
(1991)
Brachial plexus repair by peripheral nerve grafts directly into the spinal cord in rats
J. Neurosurg.
Anatomical basis of rat brachial plexus reconstruction
Surg. Radiol. Anat.
Sensoriomotor function and neuropathology 5–6 weeks after hypoxia-ischemia in 7-day-old rats
Pediatr. Res.
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