Hyperglycemia Increases Neurological Damage and Behavioral Deficits From Post-Traumatic Secondary Ischeie Insults

Abstract

The effects of post-traumatic administration of glucose 2.0 g/kg was compared to saline infusion with and without control of brain temperature at 37 degrees C on behavioral and histological measures of brain injury after controlled cortical impact injury complicated by a secondary ischemic insult. The glucose infusion increased blood glucose concentration from 114 +/- 4 to 341 +/- 76 mg/dl prior to the secondary ischemic insult. The resulting outcome measures were significantly worse in the glucose infusion group than in either control group. Mortality rate was significantly increased by the glucose administration, from 0% to 55% (p < 0.001). The median contusion volume was increased from 7.9 to 64.2 by glucose administration (p < 0.001) and the neuronal loss in the CA1 and CA3 areas of the hippocampus were greater in the glucose infusion group. In the animals that survived for the 2 weeks of behavioral studies, the duration of beam balance was shorter; the percent of animals that could balance on the beam for at least 60 s was less, the percent of animals that could perform the beam-walking task was less, and the length of time required to find the platform in the Morris water maze task was longer in the glucose infusion group. These studies demonstrate that the infusion of glucose after the cortical impact injury significantly increases the damage caused by post-traumatic ischemic insults. The adverse effect on neurological outcome could not be explained by the temperature effects of glucose infusion.

Moderate Hypothermia Improves Neurobehavioral Deficits after an Epidural Focal Mass Lesion in Rodents

“…Therefore, swimming latency was chosen as the only paradigm for cognitive assessment in the water maze test. With the balloon expansion model, it was possible to provoke reproducible cognitive deficits as known from other vessel occlusion (Alexis et al, 1995;Jaspers et al, 1990) or trauma models (Cherian et al, 1998;Dixon et al, 1998;Hamm et al, 1992;Markgraf et al, 2001). Cognitive deficits improved over the whole observation time in noncooled animals, but swimming latencies remained clearly prolonged compared to controls or hypothermic animals.…”

Cyclosporine-A-mediated inhibition of p-glycoprotein increases methylprednisolone entry into the central nervous system

“…11 Similarly, methylprednisolone-induced hyperglycemia may contribute to secondary neurologic injury. Animal models have demonstrated that hyperglycemia is an important contributor to secondary neurologic injury, 12,25 and hyperglycemia has been implicated as a contributor to poor neurologic outcome in humans. 26,27 For example, Lam et al 27 observed that head-injured patients with a postoperative blood glucose concentration greater than 200 mg/dl had a significantly worse neurologic outcome than did patients with a lower blood glucose concentration.…”

“…Specifically, the incidence of wound infection, sepsis, pneumonia, and the duration of intensive care unit stay are all increased in patients receiving high-dose methylprednisolone. [5][6][7][8] Importantly, some methylprednisolone-mediated morbidities/side effects put patients at increased risk of complications known to contribute to secondary neurological injury (eg, sepsis-induced hypotension, [9][10][11] glucocorticoid-medicated hyperglycemia 12 ). Consequently, methylprednisolone-related side effects may actually work at crosspurposes to any salutary neurological benefits of methylprednisolone therapy.…”

Is Hypothermia Useful in Managing Critically Ill Patients? Which Ones? Under What Conditions?

“…This could enhance susceptibility to infection and also might exacerbate secondary brain injury. [33][34][35] Tight glycemic control may be warranted, although the recent work by Vespa and associates suggests caution and use of insulin at higher glucose levels of probably more than 150 mg/dL. 36 Drug metabolism is profoundly altered by hypothermia.…”