Role of Glycemia in Acute Spinal Cord Injury: Data from a Rat Experimental Model and Clinical Experience

Abstract

While experimental and clinical evidence indicates that in brain injury blood glucose increases with injury severity and hyperglycemia worsens neurological outcome, the role of blood glucose in secondary mechanisms of neuronal damage after acute spinal cord injury has not yet been investigated. Data from spinal cord ischemia models suggests a deleterious effect of hyperglycemia, likely due to enhanced lactic acidosis, which is primarily dependent on the amount of glucose available to be metabolized. The purpose of this study is to summarize preliminary experimental and clinical observations on the role of blood glucose in acute spinal cord injury. Between 1995 and 1996 we used the New York University (NYU) rat spinal cord injury model to test the following hypotheses: 1) Blood glucose levels increase with injury severity. 2) Fasting protects from hyperglycemia and prevents secondary damage to the spinal cord. 3) Postinjury-induced hyperglycemia (dextrose 5% 2 gm/Kg) enhances spinal lesion volume. From a clinical perspective, we reviewed blood glucose records of 47 patients admitted to the Department of Neurosrgery in Verona, between 1991 and 1995, within 24 hours of acute spinal cord injury in order to determine: a) the incidence of hyperglycemia (> 140 mg/dl); b) the correlation between blood glucose and injury severity; and c) the role of methylprednisolone in affecting blood glucose. Results indicate that in a graded spinal cord injury model: 1) Early after injury, more severe contusions support significantly higher blood glucose levels. 2) Fasting overnight does not directly affect spinal cord lesion volume but influences blood gases, and we observed that a slightly systemic acidosis plays a minor neuroprotective role. Fasting also ensures more consistent normoglycemic baseline blood glucose values. 3) Postinjury-induced moderate hyperglycemia (160-190 mg/dl) does not significantly affect spinal cord injury. In the clinical study, we observed that during the first 24 hours after spinal cord injury: a) Glycemia ranges between 90 and 243 mg/dl (mean value 143 mg/dl), and close to 50% of the patients present blood glucose values higher than normal. b) Methylprednisolone administration is not associated to significantly higher blood glucose levels. c) There is a trend for larger glucose rises with more severe injury.

Electrophysiological changes in isolated spinal cord white matter in response to oxygen deprivation

“…This is consistent with the previous observation that glucose given after hypoxic ischemia does not affect brain injury in piglets. 26 Furthermore, it has been suggested that glucose may worsen the outcome of functional recovery following ischemic injury, 27,28 possibly through the promotion of an intracellular lactic acidosis where associated hydrogen ions are injurious to neurons and glia. 29 Membrane potential depolarization is likely due to ionic imbalances across the axonal membrane as a result of lower energy levels, which stem from oxygen deprivation.…”

Pyruvate Dehydrogenase Kinase-mediated Glycolytic Metabolic Shift in the Dorsal Root Ganglion Drives Painful Diabetic Neuropathy

“…This lactate is involved in the pathogenesis of diverse neurodegenerative diseases (91)(92)(93). Similarly, augmented lactate accumulation has been identified as one of the most important deleterious effects of hyperglycemia (94). It has been well documented that patients with diabetes frequently exhibit increased blood lactic acid levels with decreased pH (95,96).…”

Assessing the correlation of trauma severity, blood sugar level, and neurologic outcomes in traumatic spinal cord injury patients

“…Severe SCI and C. Control group. 10 All the subjects underwent routine glucose control consisting of serial blood glucose checks during the initial 24 h after the injury, comparing the recorded results showed a direct relation between BS level and severity of trauma outcomes, besides, examining the arterial blood pH and blood gas saturation level, and also evaluating the impact of insulin therapy on the mortality rate, demonstrated the little neuroprotective effect of low blood acidosis rate. It also showed that insulininduced reduction of BS level had no effect on the clinical outcome but further studies are recommended to examine the correlation of hyperglycemia and SCI.…”

“…It also showed that insulininduced reduction of BS level had no effect on the clinical outcome but further studies are recommended to examine the correlation of hyperglycemia and SCI. 10 SCI, proceeding from accidents and falling, etc. as other type of trauma is influenced by the sympathoadrenal system, leading to increased BS level.…”