Research reportEarly care of acute hyperglycemia benefits the outcome of traumatic brain injury in rats
Introduction
Traumatic brain injury (TBI) is a leading cause of death and disability, and proper early care would greatly improve the outcomes of TBI patients (Brazinova et al., 2015, Rusnak et al., 2007). Rapid resuscitation to achieve normal blood pressure, adequate oxygenation, fluid management, monitoring and normoventilation as well as thrombelastometry measurements significantly improved Intensive Care Unit survival rate and the rate of favorable outcome (Brazinova et al., 2015, Rusnak et al., 2007). Therefore, early care has an important role in achieving overall improvement in outcomes of TBI.
Acute hyperglycemia, which was defined as increase in blood glucose over 11.1 mmol/l (200 mg/dl) in the first 48 h after TBI(Melo et al., 2010), was always observed after TBI in the clinic (Azevedo et al., 2007, Melo et al., 2010, Pentelenyi, 1992). However, opinions about whether acute hyperglycemia following TBI should be considered as another measurement of early care were conflicting (Hill et al., 2010, Moro et al., 2013, Shijo et al., 2015). Several researchers indicated that acute hyperglycemia contributes to poor outcome of TBI patients and suggested its proper control in clinic (Jeremitsky et al., 2005, Lam et al., 1991, Liu-DeRyke et al., 2009, Rovlias and Kotsou, 2000, Yang et al., 1995), while others argued that acute hyperglycemia was a compensatory action of the human body after TBI and was unrelated to the outcome of patients (Hill et al., 2010, Moro et al., 2013, Shijo et al., 2015). The conflicting relationship between outcomes and acute hyperglycemia following TBI hindered proper management of the latter.
To resolve this conflict, we carefully examined previous references and found that the most positive judgment of a relationship between poor outcome and acute hyperglycemia came from clinical observations (Jeremitsky et al., 2005, Lam et al., 1991, Liu-DeRyke et al., 2009, Rovlias and Kotsou, 2000, Yang et al., 1995), while the most negative ones came from animal studies (Hill et al., 2010, Moro et al., 2013, Shijo et al., 2015) in which acute hyperglycemia following TBI was not induced by TBI itself but by extra administration of glucose or breaking of pancreatic β cells (Hill et al., 2010, Moro et al., 2013, Shijo et al., 2015). These animal studies ignored the possible internal relationship between TBI and hyperglycemia that might be the source of conflict. Therefore, we tried to examine whether acute hyperglycemia could be induced by TBI itself and treating it could benefit the outcomes of TBI, using our spontaneous acute hyperglycemia rat model (Fig. 1).
Section snippets
Striking depth could affect the level of blood glucose
Depth of TBI could influence the level of blood glucose (Fig. 2A). Striking with depths of 3.5 mm, 3.75 mm, 4.0 mm and 4.25 mm at right occipitoparietal brain could induce acute hyperglycemia of different severity. However, acute hyperglycemia induced by striking at all depths shared the same time course, peaked at 12 h and maintained a high level at 24 h. At 12 h after TBI, comparison of blood glucose levels in the different striking depth groups revealed that the 3.75 mm, 4.0 mm and 4.25 mm groups were
Discussion
Acute hyperglycemia worsened the outcomes of some types of brain injury, such as intracerebral hemorrhage (Bejot et al., 2012) and stroke (Parsons et al., 2002). Hyperglycemia was believed to induce oxygen radicals to break the blood-brain barrier and induce inflammatory factors resulting in cell death as well as apoptosis by enhancing the intracellular calcium (Song et al., 2003). Therefore, exogenous insulin was adopted to control the level of blood glucose in case of relatively low level of
Animals and materials
Eighty adult male Sprague-Dawley rats weighing 350–400 g were used. The animals were group-housed and maintained in a 12/12 h light/dark cycle with access to food and water. All experimental procedures were approved by the Institutional Animal Care and Use Committee, and conducted in accordance with the recommendations provided in the Guide for the Care and Use of Laboratory Animals.
Injury of controlled cortical impact (CCI)
The rats were initially anesthetized with 5% isoflurane and a 1:1 mixture of N2O/O2. While being maintained under
Funding
This work was supported by the Department of Public Health of Jiangsu Province [grant number H201462].
References (26)
Animal models of head trauma
NeuroRx
(2005)- et al.
Brain glycogen in health and disease
Mol. Asp. Med.
(2015) - et al.
Glucose administration after traumatic brain injury improves cerebral metabolism and reduces secondary neuronal injury
Brain Res.
(2013) - et al.
Metabolic alterations in patients who develop traumatic brain injury (TBI)-induced hypopituitarism
Growth Horm. IGF Res.
(2013) - et al.
Glucose administration after traumatic brain injury exerts some benefits and no adverse effects on behavioral and histological outcomes
Brain Res.
(2015) - et al.
Clinical significance of admission hyperglycemia and factors related to it in patients with acute severe head injury
Surg. Neurol.
(1995) - et al.
Intensive insulin therapy versus conventional glycemic control in patients with acute neurological injury: a prospective controlled trial
Arq. Neuropsiquiatr.
(2007) - et al.
The deleterious effect of admission hyperglycemia on survival and functional outcome in patients with intracerebral hemorrhage
Stroke
(2012) - et al.
Factors that may improve outcomes of early traumatic brain injury care: prospective multicenter study in Austria
Scand. J. Trauma Resusc. Emerg. Med.
(2015) - et al.
Therapeutic benefit of intravenous administration of bone marrow stromal cells after cerebral ischemia in rats
Stroke
(2001)
Implementation of a safe and effective insulin infusion protocol in a medical intensive care unit
Diabetes Care
Intraoperative hyperglycemia during liver resection: predictors and association with the extent of hepatocytes injury
PLoS One
High blood glucose does not adversely affect outcome in moderately brain-injured rodents
J. Neurotrauma
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Xin Kang, Yuepeng Liu, Tao Yuan contribute to the project equally.