Cerebral acid—base homeostasis after severe traumatic brain injury

Clausen, Tobias; Khaldi, Ahmad; Zauner, Alois; Reinert, Michael; Doppenberg, Egon M.R.; Menzel, M.; Soukup, Jens; Alves, Óscar L.; Bullock, M. Ross

doi:10.3171/jns.2005.103.4.0597

Cited by 64 publications

(70 citation statements)

References 48 publications

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“…1) Increased astrocytic glycolysis as a result of increased excitatory amino acid, chiefly glutamate, necessitates rapid uptake from the ECF via Na ϩ -dependent co-transport. The resultant intracellular glutamate and Na ϩ increase activates Na ϩ /K ϩ -ATPase, which stimulates astrocytic glycolysis and production of lactate (20,(41)(42)(43). 2) Although less likely in the present study (i.e.…”

Section: Discussionmentioning

confidence: 48%

Lactate Storm Marks Cerebral Metabolism following Brain Trauma

Lama

Auer

Tyson

et al. 2014

Journal of Biological Chemistry

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Background: In brain metabolism, neurons are fueled by lactate passed to them by glia in a metabolic coupling. Results: Following brain trauma, lactate uptake into neurons from glia was impaired, producing a metabolic lactate storm. Conclusion: Brain trauma results in neuronal-glial metabolic uncoupling, releasing free lactate. Significance: Inhibition of lactate production or its removal may be an important therapeutic strategy for brain trauma.

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Section: Discussionmentioning

confidence: 48%

Lactate Storm Marks Cerebral Metabolism following Brain Trauma

Lama

Auer

Tyson

et al. 2014

Journal of Biological Chemistry

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“…15,20 It has also been previously demonstrated that following human TBI, acidosis is associated with deranged lactate metabolism and increased mortality. 18,21,22 However, the relationship between hypoxia and acidosis and their impact on energy metabolism, including other biochemical markers, in our view warrants further exploration. The aim of the present study was, therefore, to test the hypothesis that the presence of cerebral acidosis with or without hypoxia indicates a more profound metabolic derangement, compared with the periods of hypoxia without acidosis or when normal oxygenation and pH are present.…”

Section: Introductionmentioning

confidence: 79%

“…Although many of the mechanisms above rely on intracellular pH changes, it has been shown that an intracellular pH is strongly dependent on the regulation of extracellular pH. 13 Despite differences in the methods of measurement, there is ample evidence in human studies as well as in experimental models of ischemia, 14,15 for the temporary reduction in cerebral extracellular pH (pH bt ) after cerebral insults such as TBI [16][17][18][19] and subarachnoid hemorrhage. 15,20 It has also been previously demonstrated that following human TBI, acidosis is associated with deranged lactate metabolism and increased mortality.…”

Section: Introductionmentioning

confidence: 99%

Extracellular Brain Ph with or without Hypoxia is a Marker of Profound Metabolic Derangement and Increased Mortality after Traumatic Brain Injury

Timofeev

Nortje

Al-Rawi

et al. 2012

J Cereb Blood Flow Metab

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Cerebral hypoxia and acidosis can follow traumatic brain injury (TBI) and are associated with increased mortality. This study aimed to evaluate a relationship between reduced pH bt and disturbances of cerebral metabolism. Prospective data from 56 patients with TBI, receiving microdialysis and Neurotrend monitoring, were analyzed. Four tissue states were defined based on pH bt and P bt O 2 : 1-low P bt O 2 /pH bt , 2-low pH bt /normal P bt O 2 , 3-normal pH bt /low P bt O 2 , and 4-normal pH bt /P bt O 2 ). Microdialysis values were compared between the groups. The relationship between P bt O 2 and lactate/pyruvate (LP) ratio was evaluated at different pH bt levels. Proportional contribution of each state was evaluated against mortality. As compared with the state 4, the state 3 was not different, the state 2 exhibited higher levels of lactate, LP, and glucose and the state 1-higher LP and reduced glucose (Po0.001). A significant negative correlation between LP and P bt O 2 (rho ¼ À 0.159, Po0.001) was stronger at low pH bt (rho ¼ À 0.201, Po0.001) and nonsignificant at normal pH bt (P ¼ 0.993). The state 2 was a significant discriminator of mortality categories (P ¼ 0.031). Decreased pH bt is associated with impaired metabolism. Measuring pH bt with P bt O 2 is a more robust way of detecting metabolic derangements.

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“…Having their terminals outside the blood-brain barrier and exposed to circulating pathogens and toxins, magnocellular neurons are positioned to be sentinel monitors and first defenders, modulating the innate immune response and protecting the CNS from injury. A more complete understanding of the neural networks and molecular and cellular changes involved could enhance recovery of patients after traumatic brain injury in which acidosis leads to neuronal death (23,100), with an elevated lactate/pyruvate ratio in microdialysates predictive of a less favorable outcome (70). Identifying a mechanism and site of osmotic protection will likewise benefit trauma patients, particularly those with hemorrhagic shock, in which HS provides a more balanced inflammatory response and may attenuate life-threatening multiorgan dysfunction (90).…”

Section: Perspectives and Significancementioning

confidence: 99%

“…Acidosis is a major factor spreading brain damage following ischemia and traumatic head injury in humans. Resulting from failure to maintain cellular ATP levels with loss of membrane integrity, the induced ionic imbalances produce metabolic acids that decrease both intracellular and extracellular pH adjacent to the cerebral infarct (100) and the traumatized brain (23). To our knowledge, this is the first report showing activation of the brain's innate immune response by microdialyzing an acidic perfusion fluid in the SON area, thereby identifying a new animal model for probing the pathophysiology and recovery from acidosis following injury by stroke and trauma.…”

mentioning

confidence: 99%

Peripheral osmotic stimulation inhibits the brain's innate immune response to microdialysis of acidic perfusion fluid adjacent to supraoptic nucleus

Summy-Long

2009

American Journal of Physiology-Regulatory, Integrative and Comp

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Summy-Long JY, Hu S. Peripheral osmotic stimulation inhibits the brain's innate immune response to microdialysis of acidic perfusion fluid adjacent to supraoptic nucleus. Am J Physiol Regul Integr Comp Physiol 297: R1532-R1545, 2009. First published September 16, 2009 doi:10.1152/ajpregu.00340.2009.-During the brain's innate immune response microglia, astroglia and ependymal cells resolve/repair damaged tissue and control infection. Released interleukin-1␤ (IL-1␤) reaching cerebroventricles stimulates circumventricular organs (CVOs; subfornical organ, SFO; organum vasculosum lamina terminalis, OVLT), the median preoptic nucleus (MePO), and magnocellular and parvocellular neurons in the supraoptic (SON) and paraventricular (PVN) nuclei. Hypertonic saline (HS) also activates these osmosensory CVOs and neuroendocrine systems, but, in contrast to IL-1␤, inhibits the peripheral immune response. To examine whether the brain's innate immune response is attenuated by osmotic stimulation, sterile acidic perfusion fluid was microdialyzed (2 l/ min) in the SON area of conscious rats for 6 h with sterile HS (1.5 M NaCl) injected subcutaneously (15 ml/kg) at 5 h. ϩ ; amoeboid/hypertrophied; IL-1␤ ϩ ) in the adjacent SON and bilaterally in perivascular areas of the PVN, periventricular hypothalamus and ependyma, coincident with c-Fos expression in ependymal cells and COX-2 in the vasculature. These microglial responses were attenuated by HS, coincident with activating parvocellular and magnocellular neuroendocrine systems and elevating circulating IL-1␤, oxytocin, and vasopressin. Acidosis-induced cellular injury from microdialysis activated the brain's innate immune response by a mechanism inhibited by peripheral osmotic stimulation. hypertonic saline; interleukin-1␤; acidosis; magnocellular neurons; c-Fos MICRODIALYSIS OF BRAIN NUCLEAR sites is used widely to monitor endogenous neural activity (28) and, more selectively, the central release of oxytocin and vasopressin from dendrites and somas of magnocellular neurons in the supraoptic nucleus (SON) spatially separated from their axon terminals in the neural lobe (68,73). Using this method in conscious rats, we found previously that basal release of interleukin-1␤ (IL-1␤) into dialysates (121) of the SON area increased in response to osmotic stimulation (106). Originally, the present immunohistochemical study was designed to identify local cellular sources of the cytokine (IL-1␤ ϩ ) and its biologic targets expressing the IL-1 type 1 receptor (IL-1R; 101) and having cyclooxygenase (COX-2) (65) or c-Fos induced by the cytokine (32, 60, 62). Our attention, however, widened to include the brain's innate immune response when our microdialysis studies showed activation of microglia in the SON (106).Like other tissues, an innate immune system in the brain responds to injury, protecting against infection and repairing damage in an effort to restore function (74, 87). Largely excluded from circulating blood cells and the peripheral immune system, the brain relies on glia and epend...

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Cerebral acid—base homeostasis after severe traumatic brain injury

Cited by 64 publications

References 48 publications

Lactate Storm Marks Cerebral Metabolism following Brain Trauma

Lactate Storm Marks Cerebral Metabolism following Brain Trauma

Extracellular Brain Ph with or without Hypoxia is a Marker of Profound Metabolic Derangement and Increased Mortality after Traumatic Brain Injury

Peripheral osmotic stimulation inhibits the brain's innate immune response to microdialysis of acidic perfusion fluid adjacent to supraoptic nucleus

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