Glucose administration after traumatic brain injury improves cerebral metabolism and reduces secondary neuronal injury

Abstract

Clinical studies have indicated an association between acute hyperglycemia and poor outcomes in patients with traumatic brain injury (TBI), although optimal blood glucose levels needed to maximize outcomes for these patients’ remains under investigation. Previous results from experimental animal models suggest that post-TBI hyperglycemia may be harmful, neutral, or beneficial. The current studies determined the effects of single or multiple episodes of acute hyperglycemia on cerebral glucose metabolism and neuronal injury in a rodent model of unilateral controlled cortical impact (CCI) injury. In Experiment 1, a single episode of hyperglycemia (50% glucose at 2 g/kg, i.p.) initiated immediately after CCI was found to significantly attenuate a TBI-induced depression of glucose metabolism in cerebral cortex (4 of 6 regions) and subcortical regions (2 of 7) as well as to significantly reduce the number of dead/dying neurons in cortex and hippocampus at 24 h post-CCI. Experiment 2 examined effects of more prolonged and intermittent hyperglycemia induced by glucose administrations (2 g/kg, i.p.) at 0, 1, 3 and 6 h post-CCI. The latter study also found significantly improved cerebral metabolism (in 3 of 6 cortical and 3 of 7 subcortical regions) and significant neuroprotection in cortex and hippocampus 1 day after CCI and glucose administration. These results indicate that acute episodes of post-TBI hyperglycemia can be beneficial and are consistent with other recent studies showing benefits of providing exogenous energy substrates during periods of increased cerebral metabolic demand.

Low-Level Light in Combination with Metabolic Modulators for Effective Therapy of Injured Brain

“…30 However, lactate and pyruvate can readily cross the blood-brain barrier and enter the tricarboxylic acid cycle, 31,32 being preferential oxidative energy substrates over glucose for neurons. 33,34 The beneficial effect of exogenous glucose, lactate, and pyruvate has been shown in some TBI models, [35][36][37] but these substrates only modestly reduce the lesion size, with no apparent functional protection in our model. However, when lactate or pyruvate is combined with LLL illumination, mitochondrial functions are improved either additively or synergistically, giving rise to a faster recovery and less brain tissue loss compared with LLL, pyruvate, or lactate alone.…”

Stress-induced hyperglycemia is associated with higher mortality in severe traumatic brain injury

“…27,28 This has led investigators to theorize that endogenous levels of glucose may not be sufficient to meet increased energy consumption of the injured brain, which may result in a metabolic secondary injury. Moro et al 15 provide support for this hypothesis in a rodent model of controlled cortical impact where exogenous glucose initiated after injury provided significant cellular neuroprotection and improved cerebral metabolism. Likewise, Hill et al 14 examined the effects of persistent hyperglycemia as seen in diabetic patients, on animals that were treated with streptozotocin to induce Type 1 diabetes.…”

Glucose administration after traumatic brain injury exerts some benefits and no adverse effects on behavioral and histological outcomes

“…The multiple glucose injections also resulted in a significant prevention of cortical tissue loss at 15 days post-CCI. Because these doses of glucose increase blood glucose levels to between 17.0 and 19.5 mmol/L (Moro et al, 2013), the current results suggest that an acute period of hyperglycemia after experimental TBI may improve some neurological outcomes and, importantly, it exerts no detrimental effects in a rat model of TBI.…”

“…Lower doses of glucose (100 mg/kg) administered from 1–10 days after fluid percussion brain injury did not alter cognitive outcome 11–15 post-injury (Kokiko-Cochran et al, 2008). More recently, single or multiple injections of hyperglycemic doses of glucose within the first 6 hours after CCI injury were found to significantly attenuate TBI-induced reductions in CMRGlc and reduce neuronal injury in cortex and hippocampus at 24 h post-injury (Moro et al, 2013). …”

“…Recovery on sensorimotor and cognitive tasks were determined over a 2 week period, and cortical contusion volume and surviving neurons in the hilar region of the hippocampus were determined at 15 days post-CCI. Based on benefits seen with this glucose treatment regimen by 24 h post-CCI (Moro et al, 2013), we hypothesized that acute hyperglycemia would be beneficial for behavioral recovery and improve histological outcomes at 2 weeks post-injury.…”