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

Abstract

The impact of hyperglycemia after traumatic brain injury (TBI), and even the administration of glucose-containing solutions to head injured patients, remains controversial. In the current study adult male Sprague-Dawley rats were tested on behavioral tasks and then underwent surgery to induce sham injury or unilateral controlled cortical impact (CCI) injury followed by injections (i.p.) with either a 50% glucose solution (Glc; 2g/kg) or an equivalent volume of either 0.9% or 8% saline (Sal) at 0, 1, 3 and 6h post-injury. The type of saline treatment did not significantly affect any outcome measures, so these data were combined. Rats with CCI had significant deficits in beam-walking traversal time and rating scores (p's < 0.001 versus sham) that recovered over test sessions from 1 to 13 days post-injury (p's < 0.001), but these beam-walking deficits were not affected by Glc versus Sal treatments. Persistent post-CCI deficits in forelimb contraflexion scores and forelimb tactile placing ability were also not differentially affected by Glc or Sal treatments. However, deficits in latency to retract the right hind limb after limb extension were significantly attenuated in the CCI-Glc group (p < 0.05 versus CCI-Sal). Both CCI groups were significantly impaired in a plus maze test of spatial working memory on days 4, 9 and 14 post-surgery (p < 0.001 versus sham), and there was no effect of Glc versus Sal on this cognitive outcome measure. At 15 days post-surgery the loss of cortical tissue volume (p < 0.001 versus sham) was significantly less in the CCI-Glc group (30.0%; p < 0.05) compared to the CCI-Sal group (35.7%). Counts of surviving hippocampal hilar neurons revealed a significant (~40%) loss ipsilateral to CCI (p < 0.001 versus sham), but neuronal loss in the hippocampus was not different in the CCI-Sal and CCI-Glc groups. Taken together, these results indicate that an early elevation of blood glucose may improve some neurological outcomes and, importantly, the induction of hyperglycemia after isolated TBI did not adversely affect any sensorimotor, cognitive or histological outcomes.

Keywords: Beam-walking; Cognition; Controlled cortical impact; Contusion volume; Hippocampus; Hyperglycemia; Neurological exam; Rat; Spatial working memory.

Fig. 1

Mean (± SEM) beam traversal times for rats (n = 12/group) before (Pre) and after sham or controlled cortical impact (CCI) injury and treatments of either saline (Sal) or glucose (Glc) at 0, 1, 3 and 6 h post-surgery. There was a significant effect of Injury (p<0.001), Days (p<0.001), and the Injury x Day interaction (p<0.001), with no effects for Treatment or Treatment interactions.

Fig. 2

Mean (± SEM) beam-walk ratings for rats (n = 12/group) before (Pre) and after sham or controlled cortical impact (CCI) injury and treatments (at 0, 1, 3 and 6 h post-surgery) of either saline (Sal) or glucose (Glc). There was a significant effect of Injury (p<0.001), Days (p<0.001), and the Injury x Day interaction (p<0.001), with no effects for Treatment or Treatment interactions.

Fig. 3

Mean (± SEM) tactile placing of the right forelimb for rats (n = 12/group) after controlled cortical impact (CCI) injury and treatments of either saline (Sal) or glucose (Glc) at 0, 1, 3 and 6 h post-surgery. There was a significant effect of Days (p<0.001), but no significant effect for Treatment or the Day x Treatment interaction.

Fig. 4

Mean (± SEM) ratings of contraflexion for rats (n = 12/group) after controlled cortical impact (CCI) injury and treatments of either saline (Sal) or glucose (Glc) at 0, 1, 3 and 6 h post-surgery. There was a significant effect of Days (p<0.05), with no significant effects for Treatment or the Day x Treatment interaction.

Fig. 5

Mean (± SEM) duration to retract the right hind limb after lateral/posterior displacement in rats (n = 12/group) with controlled cortical impact (CCI) injury and treatments of either saline (Sal) or glucose (Glc) at 0, 1, 3 and 6 h post-surgery. There was a significant effect of Days (p<0.001) and Treatment (p<0.05), with no significant Day x Treatment interaction.

Fig. 6

Mean (± SEM) number of arm entries during pre- and post-surgical tests of spatial working memory for rats (n = 10/group) with sham or controlled cortical impact (CCI) injury and treatments of either saline (Sal) or glucose (Glc) at 0, 1, 3 and 6 h post-surgery. There was a significant effect of Days (p<0.001; day 9 less than day 4, p<0.01), with no effects of Injury or Treatment and no significant interactions.

Fig. 7

Mean (± SEM) percent four/five (% 4/5) alternation scores during pre- and post-surgical tests of spatial working memory for rats (n = 10/group) with sham or controlled cortical impact (CCI) injury and treatments of either saline (Sal) or glucose (Glc) at 0, 1, 3 and 6 h post-surgery. There was a significant effect of Injury (p<0.001), but no significant effects for Days, Treatment, or for any interactions.

Fig. 8

Mean (± SEM) percent tissue volume loss in the left/injured cortex (A) and mean (± SEM) cortical area at 10 equally spaced coronal sections (B) for rats (n = 12/group) with sham or controlled cortical impact (CCI) injury and treatments of either saline (Sal) or glucose (Glc) at 0, 1, 3 and 6 h post-surgery. Cortical tissue volume loss was reduced for CCI-Glc compared to CCI-Sal (* p<0.05). Photomicrographs from animals representing group means for cortical area measures at −1.4 mm from Bregma are shown for CCI-Sal (C) and CCI-Glc (D). The mean (± SEM) percent neuronal loss in the left hilus is shown for the four treatment groups (n = 8/group) in panel E. High magnification photomicrographs (scale bar of 100 μm) show polymorphic hilar neurons between the CA3c pyramidal cells (dashed line) and the inner blade of the dentate granule cells in sham injury (F) and CCI injury (G) conditions.