Neurochemical changes following combined hypoxemia and hemorrhagic shock in a rat model of penetrating ballistic-like brain injury

Leung, Lai Yee; Deng-Bryant, Ying; Cardiff, Katherine; Winter, Matthew J.; Tortella, Frank C.; Shear, Deborah A.

doi:10.1097/ta.0000000000001206

Cited by 10 publications

(9 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We also detected altered glucose uptake and oxygen consumption in the injured cortex, including both the injury core and the peri-lesional area, at 2.5 h post-PBBI (37). In addition, using intracerebral microdialysis, we have reported an early energy metabolic dysfunction and the metabolic shift toward anaerobic glycolysis (indicated by high lactate to pyruvate ratio) within 3 h following PBBI (38).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Profile of Acute Mitochondrial Dysfunction in a Preclinical Model of Severe Penetrating TBI

et al. 2019

Self Cite

View full text Add to dashboard Cite

Mitochondria constitute a central role in brain energy metabolism, and play a pivotal role in the development of secondary pathophysiology and subsequent neuronal cell death following traumatic brain injury (TBI). Under normal circumstances, the brain consumes glucose as the preferred energy source for adenosine triphosphate (ATP) production over ketones. To understand the comprehensive picture of substrate-specific mitochondrial bioenergetics responses following TBI, adult male rats were subjected to either 10% unilateral penetrating ballistic-like brain injury (PBBI) or sham craniectomy ( n = 5 animals per group). At 24 h post-injury, mitochondria were isolated from pooled brain regions (frontal cortex and striatum) of the ipsilateral hemisphere. Mitochondrial bioenergetics parameters were measured ex vivo in the presence of four sets of metabolic substrates: pyruvate+malate (PM), glutamate+malate (GM), succinate (Succ), and β-hydroxybutyrate+malate (BHBM). Additionally, mitochondrial matrix dehydrogenase activities [i.e., pyruvate dehydrogenase complex (PDHC), alpha-ketoglutarate dehydrogenase complex (α-KGDHC), and glutamate dehydrogenase (GDH)] and mitochondrial membrane-bound dehydrogenase activities [i.e., electron transport chain (ETC) Complex I, II, and IV] were compared between PBBI and sham groups. Furthermore, mitochondrial coenzyme contents, including NAD (t) and FAD (t) , were quantitatively measured in both groups. Collectively, PBBI led to an overall significant decline in the ATP synthesis rates (43–50%; * p < 0.05 vs. sham) when measured using each of the four sets of substrates. The PDHC and GDH activities were significantly reduced in the PBBI group (42–53%; * p < 0.05 vs. sham), whereas no significant differences were noted in α-KGDHC activity between groups. Both Complex I and Complex IV activities were significantly reduced following PBBI (47–81%; * p < 0.05 vs. sham), whereas, Complex II activity was comparable between groups. The NAD (t) and FAD (t) contents were significantly decreased in the PBBI group (27–35%; * p < 0.05 vs. sham). The decreased ATP synthesis rates may be due to the significant reductions in brain mitochondrial dehydrogenase activities and coenzyme contents observed acutely following PBBI. These results provide a basis for the use of “alternative biofuels” for achieving higher ATP production following severe penetrating brain trauma.

show abstract

Section: Discussionmentioning

confidence: 99%

Comprehensive Profile of Acute Mitochondrial Dysfunction in a Preclinical Model of Severe Penetrating TBI

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…22 Combined hypoxemia and hemorrhagic shock in animal models of TBI + HS have been associated with transient intracerebral reductions in brain glucose, pyruvate, and prolonged elevations of lactate. 23,24 Energy-related neurochemical dysregulation in TBI + HS is likely a major factor contributing to worse neurologic outcomes. 25 Therefore, principles of damage-control resuscitation, which include permissive hypotension, 4,5,9 require further study in patients with TBI+HS, since a higher mean arterial pressure (>70-mm Hg) may result in better cerebral blood flow and cerebral mitochondrial function.…”

Section: Discussionmentioning

confidence: 99%

“…Most studies of TBI and HS have been focused on neuronal death, 33 neurochemical changes, 23 or other physiological mechanisms, 22,24 and none have been done in humans. While the number of patients in this post hoc analysis of patients previously randomized in PROPPR yielded a modest number of patients with TBI and HS, to our knowledge, this represents the largest study population with these two conditions conducted to date.…”

Section: Discussionmentioning

confidence: 99%

Outcomes after concomitant traumatic brain injury and hemorrhagic shock

Galvagno

Fox

Appana

et al. 2017

Journal of Trauma and Acute Care Surgery

View full text Add to dashboard Cite

Background Often the clinician is faced with a diagnostic and therapeutic dilemma in patients with concomitant traumatic brain injury (TBI) and hemorrhagic shock (HS), as rapid deterioration from either can be fatal. Knowledge about outcomes following concomitant TBI and HS may help prioritize the emergent management of these patients. We hypothesized that patients with concomitant TBI and HS (TBI+HS) had worse outcomes and required more intensive care compared to patients with only one of these injuries. Methods This is a post-hoc analysis of the Pragmatic, Randomized Optimal Platelets and Plasma Ratios (PROPPR) trial. TBI was defined by a head abbreviated injury scale >2. HS was defined as a base excess ≤ −4 and/or shock index ≥ 0.9. The primary outcome for this analysis was mortality at 30 days. Logistic regression, using generalized estimating equations (GEE), was used to model categorical outcomes. Results 670 patients were included. Patients with TBI+HS had significantly higher lactate (median 6.3; IQR 4.7,9.2) compared to the TBI group (median 3.3; IQR 2.3,4). TBI+HS patients had higher activated prothrombin times and lower platelet counts. Unadjusted mortality was higher in the TBI+HS (51.6%) and TBI (50%) groups compared to the HS (17.5%) and neither group (7.7%). Adjusted odds of death in the TBI and TBI+HS groups were 8.2 (95% CI, 3.4–19.5) and 10.6 (95% CI, 4.8–23.2) times higher, respectively. Ventilator, ICU- and hospital-free days were lower in the TBI and TBI+HS groups compared to the other groups. Patients with TBI+HS or TBI had significantly greater odds of developing a respiratory complication compared to the neither group. Conclusions The addition of TBI to HS is associated with worse coagulopathy prior to resuscitation, and increased mortality. When controlling for multiple known confounders, the diagnosis of TBI alone or TBI+HS was associated with significantly greater odds of developing respiratory complications.

show abstract

“…Microdialysis (MD) is a specific, local sampling method to collect free molecules of interest from the extracellular fluid 10 . It has been used widely in both animals and human subjects to investigate the changes experienced by extracellular molecules or medicine under certain physical or pathological conditions 11 . In our hypothesis-driven study, we set up an MD system for ionic molecule detection at the acupoints in rats undergoing EA, and checked the correlation between these free-molecule levels and the photon activity in the stomach.…”

Section: Introductionmentioning

confidence: 99%

Effect of Electroacupuncture on 99mTc-Sodium Pertechnetate Uptake and Extracellular Fluid Free Molecules in the Stomach in Acupoint ST36 and ST39

Gao

Feng

et al. 2018

Sci Rep

View full text Add to dashboard Cite

Electroacupuncture (EA) is a therapeutic modality in which the electrical stimulation is integrated with concepts of acupuncture to treat diseases. This study was designed to evaluate the connection between the electro-acupuncture induced increase in Na99mTcO4 uptake in the stomach wall, and the ionic molecule levels in the extracellular fluid in the acupoints. Wistar rats were treated by 2 or 100 Hz EA at Zusanli (ST 36) and Xiajuxu (ST 39) bilaterally for 60 minutes. The accumulation of Na99mTcO4 in the gastric wall and the free ions, including Ca2+, K+, Na+, and Cl−, in the acupoints were measured every 60 minutes. The radioactivity uptake in the stomach was significantly increased during EA, reaching peak at 180 minutes after the EA. The concentration of extracellular ions was also significantly increased during EA. The Ca2+ level continued to rise until 60 minutes after EA, then started to decrease at 120 minutes post-EA. The results suggest this up-regulatory effect of EA on gastric activity might be triggered by the increase of the extracellular ion levels, this effect lasts longer than stimulating the release of transmembrane Ca2+ flow alone. This might aid in providing a better understanding of the long-lasting effect claimed in acupuncture treatment.

show abstract

Neurochemical changes following combined hypoxemia and hemorrhagic shock in a rat model of penetrating ballistic-like brain injury

Cited by 10 publications

References 39 publications

Comprehensive Profile of Acute Mitochondrial Dysfunction in a Preclinical Model of Severe Penetrating TBI

Comprehensive Profile of Acute Mitochondrial Dysfunction in a Preclinical Model of Severe Penetrating TBI

Outcomes after concomitant traumatic brain injury and hemorrhagic shock

Effect of Electroacupuncture on 99mTc-Sodium Pertechnetate Uptake and Extracellular Fluid Free Molecules in the Stomach in Acupoint ST36 and ST39

Contact Info

Product

Resources

About