Norepinephrine-induced hyperglycemia does not increase cortical lactate in brain-injured rats

Stover, John; Sakowitz, Oliver W.; Thomale, Ulrich W.; Kroppenstedt, Stefan; Unterberg, Andreas

doi:10.1007/s00134-002-1431-2

Cited by 13 publications

(6 citation statements)

References 54 publications

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“…Thus, elevating MABP in the early posttraumatic phase could have contributed to increased vasogenic edema formation via sustained hydrostatic pressure as often criticized by proponents of the "Lund" concept in the treatment of head injury (2). In this context, increases in pericontusional extracellular glutamate and glucose during norepinephrine infusion early after CCI (11,47) are suggestive of uncontrolled passive penetration. Concentration dependently, norepinephrine acts as a pro-oxidative or anti-oxidative agent (25).…”

Section: Discussionmentioning

confidence: 92%

Effects of early and late intravenous norepinephrine infusion on cerebral perfusion, microcirculation, brain-tissue oxygenation, and edema formation in brain-injured rats

Kroppenstedt

Thomale

Griebenow

et al. 2003

Critical Care Medicine

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Section: Discussionmentioning

confidence: 92%

Effects of early and late intravenous norepinephrine infusion on cerebral perfusion, microcirculation, brain-tissue oxygenation, and edema formation in brain-injured rats

Kroppenstedt

Thomale

Griebenow

et al. 2003

Critical Care Medicine

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“…Although we did not assess brain levels of glucose in the current study, we speculate that the interstitial levels were increased in our CCI rats administered glucose. Norepinephrine infusion in rats with CCI increases blood glucose (from 8.6 to 12.6 mmol/L) and extracellular glucose (from 1.3 to 4.8 mmol/L) concentrations without altering edema formation (Stover et al, 2002), and it has been reported that extracellular concentrations of glucose are significantly increased during transient periods of unintentional hyperglycemia in TBI patients (Diaz-Parejo et al, 2003). The latter authors also reported no change in interstitial concentrations of pyruvate, lactate, glutamate or glycerol with episodes of moderate hyperglycemia (blood levels of 12-15 mmol/L), although lactate levels increased during episodes of more pronounced (>15 mmol/L) hyperglycemia.…”

Section: Discussionmentioning

confidence: 99%

“…More recently it was reported that induction of hyperglycemia prior to moderate CCI injury in mice did not adversely affect cerebral edema, behavioral outcomes or histopathology, whereas chronic hyperglycemia in rats actually reduced CCI-induced cerebral edema and a post-injury insulin therapy to lower high blood glucose increased cerebral edema (Hill et al, 2010). To date, there is no evidence that post-CCI elevations in plasma glucose will exacerbate histopathology or worsen outcomes (Cherian et al, 1998a; Stover et al, 2002). …”

Section: Introductionmentioning

confidence: 99%

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

Moro¹,

Ghavim²,

Harris³

et al. 2013

Brain Research

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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.

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“…Furthermore, Kinoshita and associates showed that although acute post-traumatic dextrose treatment increased lesion area only slightly, a significant infiltration of neutrophils was seen following fluid percussion injury (FPI; Kinoshita et al, 2002). In contrast, the results of several experimental studies investigating hyperglycemia following TBI did not support adverse effects on brain damage (Gurevich et al, 1997;Hill et al, 2010;Stover et al, 2002). Clinical studies, however, show that hyperglycemia at admission is associated with poor neurological outcomes and mortality following severe TBI, both in pediatric (Melo et al, 2010;Smith, et al, 2012) and adult patients ( Jeremitsky et al, 2005;Pecha et al, 2011).…”

Section: Introductionmentioning

confidence: 87%

The Neuroprotective Effect of Lactate Is Not Due to Improved Glutamate Uptake after Controlled Cortical Impact in Rats

Alessandri

Schwandt

Kamada

et al. 2012

Journal of Neurotrauma

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For many years lactate was considered to be a waste product of glycolysis. Data are accumulating that suggest that lactate is an important energy substrate for neurons during activation. In severe traumatic brain injury (TBI) glutamate release and ischemic cerebral blood flow (CBF) are major factors for a mismatch between energy demand and supply and for neuronal cell death. Although ATP and behavior could be improved by lactate treatment after TBI, no histological correlate nor any linkage to better astrocytic glutamate uptake or CBF as possible mechanisms have been described. We subjected male rats to a controlled cortical impact (CCI; 5 m/sec, 2.5 mm). To study the effects of lactate treatment on lesion volume, glutamate release, and CBF, animals were infused with either NaCl or 100 mM lactate for up to 3 h. The role of endogenous lactate was investigated by inhibiting transport with α-cyano-4-hydroxy-cinnamic acid (4-CIN; 90 mg/kg). Lactate treatment 15 min post-CCI reduced lesion volume from 21.1±2.8 mm³ to 12.1±1.9 mm³ at day 2 after CCI. Contusion produced a significant three- to fourfold increase of glutamate in microdialysates, but there was no significant difference between treatments that began 30 min before CCI. In this experiment lesion volume was significantly reduced by lactate at day 7 post-CCI (23.7±4 to 9.3±1-2 mm³). CBF increased immediately after CCI and dropped thereafter below baseline in all animals. Lactate infusion 15 min post-CCI elevated CBF for 20 min in 7 of 10 animals, whereas 7 of 8 NaCl-treated animals showed a further CBF decline. Neuroprotection was achieved by lactate treatment following contusion injury, whereas blocking of endogenous lactate transport exerted no adverse effects. Neuroprotection was not achieved by improved glutamate uptake into astrocytes, but was supported by augmented CBF following CCI. Due to its neuroprotective property, lactate might be a beneficial pharmacological treatment for TBI patients.

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Norepinephrine-induced hyperglycemia does not increase cortical lactate in brain-injured rats

Cited by 13 publications

References 54 publications

Effects of early and late intravenous norepinephrine infusion on cerebral perfusion, microcirculation, brain-tissue oxygenation, and edema formation in brain-injured rats

Effects of early and late intravenous norepinephrine infusion on cerebral perfusion, microcirculation, brain-tissue oxygenation, and edema formation in brain-injured rats

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

The Neuroprotective Effect of Lactate Is Not Due to Improved Glutamate Uptake after Controlled Cortical Impact in Rats

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