The Correlation between Calcium Intensity and Histopathological Changes in Brachial Plexus Nerve Injuries

Abstract

Background After nerve injury, an influx of calcium exceeds the homeostatic capacity, which damages peripheral nerves. Previous studies identified that following nerve crush, function improves as calcium levels normalize.

Methods Electrophysiological analysis was performed to measure the compound muscle action potential of 15 patients' damaged nerves. These samples were evaluated for calcium level and also stained with a Luxol fast blue and neurofilament antibodies to evaluate the myelin sheath and neurofilaments of the nerves. Based on the Sunderland scale, we identified three exclusive types of peripheral nerve injury groups.

Results There was a correlation between histopathological damage and calcium levels of 0.81 (p < 0.005). The average relative fluorescence units (RFUs) was 235.28 ± 19, which corresponds to 5.3 × 10⁻⁷ M of calcium, five times the normal value.

Conclusion Our study shows promising clinical implications via faster pathology results by the RFU technique. This approach of calcium staining, though still in clinical trials, offers significant clinical application, allowing physicians to get the clinically diagnostic nerve injury degree faster and will also facilitate better strategies for further treatment or future surgeries.

Keywords

brachial plexus nerve injuries - peripheral nerve injury - relative fluorescence units - calcium nerve staining - grading peripheral nerve injuries

• References

• 1 Martinez AM, Ribeiro LC. Ultrastructural localization of calcium in peripheral nerve fibres undergoing Wallerian degeneration: an oxalate-pyroantimonate and X-ray microanalysis study. J Submicrosc Cytol Pathol 1998; 30 (3) 451-458
• 2 Sunderland S. Nerve Injuries and Their Repair: A Critical Appraisal. New York: Churchill Livingstone; 1991
• 3 Gleichmann M, Mattson M. Neuronal calcium homeostasis and dysregulation. Antioxid Redox Signal 2011; (7) 1261-1273
• 4 Arundine M, Tymianski M. Molecular mechanisms of calcium-dependent neurodegeneration in excitotoxicity. Cell Calcium 2003; 34 (4–5) 325-337
• 5 Sattler R, Tymianski M, Feyaz I, Hafner M, Tator CH. Voltage-sensitive calcium channels mediate calcium entry into cultured mammalian sympathetic neurons following neurite transection. Brain Res 1996; 719 (1–2) 239-246
• 6 Ziv NE, Spira ME. Axotomy induces a transient and localized elevation of the free intracellular calcium concentration to the millimolar range. J Neurophysiol 1995; 74 (6) 2625-2637
• 7 Orrenius S, Nicotera P. The calcium ion and cell death. J Neural Transm Suppl 1994; 43: 1-11
• 8 Mayoux-Benhamou MA, Revel M, Vallee C. Selective electromyography of dorsal neck muscles in humans. Exp Brain Res 1997; 113 (2) 353-360
• 9 Yan JG, Matloub HS, Yan Y, Agresti M, Zhang LL, Jaradeh SS. The correlation between calcium absorption and electrophysiological recovery in crushed rat peripheral nerves. Microsurgery 2010; 30 (2) 138-145
• 10 Lee SK, Wolfe SW. Peripheral nerve injury and repair. J Am Acad Orthop Surg 2000; 8 (4) 243-252
• 11 Yan J-G, Eldridge MP, Dzwierzynski WW , et al. Intraoperative electrophysiological studies to predict the efficacy of neurolysis after nerve injury-experiment in rats. Hand (NY) 2008; 3 (3) 257-262
• 12 Spitzer NC, Gu X, Olson E. Action potentials, calcium transients and the control of differentiation of excitable cells. Curr Opin Neurobiol 1994; 4 (1) 70-77
• 13 Yuste R, Katz LC. Control of postsynaptic Ca2+ influx in developing neocortex by excitatory and inhibitory neurotransmitters. Neuron 1991; 6 (3) 333-344
• 14 Blaustein MP. Calcium transport and buffering in neurons. Trends Neurosci 1988; 11 (10) 438-443
• 15 Stys PK, Ransom BR, Waxman SG, Davis PK. Role of extracellular calcium in anoxic injury of mammalian central white matter. Proc Natl Acad Sci U S A 1990; 87 (11) 4212-4216
• 16 Kiedrowski LG, Brooker G, Costa E, Wroblewski JT. Glutamate impairs neuronal calcium extrusion while reducing sodium gradient. Neuron 1994; 12 (2) 295-300
• 17 Mattson MP, Guthrie PB, Kater SB. A role for Na + -dependent Ca2+ extrusion in protection against neuronal excitotoxicity. FASEB J 1989; 3 (13) 2519-2526
• 18 Stys PK, Waxman SG, Ransom BR. Ionic mechanisms of anoxic injury in mammalian CNS white matter: role of Na+ channels and Na(+)-Ca2+ exchanger. J Neurosci 1992; 12 (2) 430-439
• 19 Tymianski M, Tator CH. Normal and abnormal calcium homeostasis in neurons: a basis for the pathophysiology of traumatic and ischemic central nervous system injury. Neurosurgery 1996; 38 (6) 1176-1195
• 20 Nielsen VK, Osgaard O, Trojaborg W. Interfascicular neurolysis in chronic ulnar nerve lesions at the elbow: an electrophysiological study. J Neurol Neurosurg Psychiatry 1980; 43 (3) 272-280
• 21 Deletis V, Morota N, Abbott IR. Electrodiagnosis in the management of brachial plexus surgery. Hand Clin 1995; 11 (4) 555-561
• 22 Goldberg MP, Giffard RG, Kurth MC, Choi DW. Role of extracellular calcium and magnesium in ischemic neuronal injury in vitro. [abstract] Neurology 1989; 39 (Suppl): 217
• 23 LoPachin RM, Lehning EJ. Mechanism of calcium entry during axon injury and degeneration. Toxicol Appl Pharmacol 1997; 143 (2) 233-244
• 24 Manev H, Favaron M, Guidotti A, Costa E. Delayed increase of Ca2+ influx elicited by glutamate: role in neuronal death. Mol Pharmacol 1989; 36 (1) 106-112
• 25 de Medinaceli L, Church AC. Peripheral nerve reconnection: inhibition of early degenerative processes through the use of a novel fluid medium. Exp Neurol 1984; 84 (2) 396-408
• 26 Lucas JH, Gross GW, Emery DG, Gardner CR. Neuronal survival or death after dendrite transection close to the perikaryon: correlation with electrophysiologic, morphologic, and ultrastructural changes. Cent Nerv Syst Trauma 1985; 2 (4) 231-255
• 27 Shi RY, Lucas JH, Wolf A, Gross GW. Calcium antagonists fail to protect mammalian spinal neurons after physical injury. J Neurotrauma 1989; 6 (4) 261-276 , discussion 277–278
• 28 Liu WT, Vanguri P, Shin ML. Studies on demyelination in vitro: the requirement of membrane attack components of the complement system. J Immunol 1983; 131 (2) 778-782
• 29 Brück W, Brück Y, Diederich U, Piddlesden SJ. The membrane attack complex of complement mediates peripheral nervous system demyelination in vitro. Acta Neuropathol 1995; 90 (6) 601-607 DOI: 10.1007/BF00318572.
• 30 Mead RJ, Singhrao SK, Neal JW, Lassmann H, Morgan BP. The membrane attack complex of complement causes severe demyelination associated with acute axonal injury. J Immunol 2002; 168 (1) 458-465
• 31 Stoll G, Griffin JW, Li CY, Trapp BD. Wallerian degeneration in the peripheral nervous system: participation of both Schwann cells and macrophages in myelin degradation. J Neurocytol 1989; 18 (5) 671-683 DOI: 10.1007/BF01187086.