Lactate and pH in the Brain: Association and Dissociation in Different Pathophysiological States

Paschen, Wulf; Djuričić, Bogdan; Mies, Günter; Schmidt‐Kastner, Rainald; Linn, F.

doi:10.1111/j.1471-4159.1987.tb13140.x

Cited by 172 publications

(81 citation statements)

References 45 publications

(23 reference statements)

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“…Alterations in brain pH and lactate can arise as a consequence of agonal state (e.g. by cerebral ischaemia or hypoxia: Wester et al 1985;Paschen et al 1987). In neurodegenerative diseases, pH change may arise from compromised energy metabolism and as a consequence of an increased glial neurone ratio in areas of tissue damage.…”

Section: Tissue Phmentioning

confidence: 99%

Biochemical and molecular studies using human autopsy brain tissue

Hynd

Lewohl

Scott

et al. 2003

Journal of Neurochemistry

220

171

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The use of human brain tissue obtained at autopsy for neurochemical, pharmacological and physiological analyses is reviewed. RNA and protein samples have been found suitable for expression profiling by techniques that include RT-PCR, cDNA microarrays, western blotting, immunohistochemistry and proteomics. The rapid development of molecular biological techniques has increased the impetus for this work to be applied to studies of brain disease. It has been shown that most nucleic acids and proteins are reasonably stable postmortem. However, their abundance and integrity can exhibit marked intra-and intercase variability, making comparisons between case-groups difficult. Variability can reveal important functional and biochemical information. The correct interpretation of neurochemical data must take into account such factors as age, gender, ethnicity, medicative history, immediate ante-mortem status, agonal state and post-mortem and post-autopsy intervals. Here we consider issues associated with the sampling of DNA, RNA and proteins using human autopsy brain tissue in relation to various ante-and postmortem factors. We conclude that valid and practical measures of a variety of parameters may be made in human brain tissue, provided that specific factors are controlled.

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Section: Tissue Phmentioning

confidence: 99%

Biochemical and molecular studies using human autopsy brain tissue

Hynd

Lewohl

Scott

et al. 2003

Journal of Neurochemistry

220

171

View full text Add to dashboard Cite

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“…It must be emphasized that hypoxia-ischemia leads to cellular acidosis via sources of H+ ions in addition to lactic acid. Possibly the major origin of reducing equivalents is NADH (+ H+) which accumulates during cellular oxygen debt (55). In this regard, Welsh et al (15) examined the redox state of immature rat brain undergoing hypoxia-ischemia by a technique of reflectance fluorometry.…”

Section: Y~o S O~mentioning

confidence: 99%

Experimental Biology of Cerebral Hypoxia-Ischemia: Relation to Perinatal Brain Damage

1990

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ABSTRACT. Cerebral hypoxia-ischemia remains a major cause of acute perinatal brain injury, leading ultimately to neurologic dysfunction manifest as cerebral palsy, mental retardation, and epilepsy. Research in experimental animals over the past 10 or more years has expanded greatly our understanding of the cellular and molecular events that occur during a hypoxic-ischemic insult to brain, and recent discoveries have suggested that metabolic pertubations arising in the recovery period after resuscitation contribute substantially to the nature and extent of neuronal destruction. The review focuses on those neurochemical processes responsible for the maintenance of cellular homeostasis and how these mechanisms fail in hypoxia-ischemia to culminate in brain damage. Knowledge of these critical events has opened new avenues of potential therapy for the fetus and newborn infant subjected to cerebral hypoxiaischemia to prevent the serious delayed effects of perinatal brain injury. Perinatal cerebral hypoxia-ischemia typically is initiated by compromised placental or pulmonary gas exchange which leads to systemic hypoxia/anoxia with or without concurrent hypercapnia (asphyxia) (1). Hypoxia/hypercapnia increases CBF adequate to maintain brain metabolism stable until cerebral ischemia supervenes owing to cardiac depression with secondary bradycardia and systemic hypotension. With the neuronal oxygen and glucose debt arising from ischemia, oxidative metaboReceived August 16, 1989; accepted November 30, 1989. Supported by Grants HD-09 109, HD-15738, HD-199 13, and HL-19190 from the NIH and by grants from the American Heart Association and American Diabetes Association. lism shifts to anaerobic glycolysis with its inefficient generation of high-energy phosphate reserves necessary to maintain cellular ionic gradients and other metabolic processes. Ultimately, cellular energy failure occurs, which, if not promptly reversed, results in death of the cell.Over the past decade, a wealth of research has expanded our knowledge of those critical cellular metabolic events that eventually lead to tissue injury arising from hypoxia-ischemia. Investigations have shown that hypoxia-ischemia sets in motion a cascade of biochemical alterations that are initiated during the course of the insult and that proceed well into the recovery period after resuscitation. This review will highlight those cellular processes involved in this metabolic cascade and how they evolve into perinatal hypoxic-ischemic brain damage. CELLULAR ENERGY TRANSFORMATIONSATP is the primary energy modulator of the cell (2-4). Its two -P exist at an energy level capable of providing the necessary driving force for innumerable biochemical reactions and physiologic processes. ATP not only promotes energy consuming reactions but also drives physiologic processes (e.g. ion pumping) by acid hydrolysis. As such, the compound provides the cellular free energy necessary to maintain neuronal viability with its specialized function.Under physiologic conditions, cellular ATP is maint...

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“…Activation by aluminum is optimal at an acidic pH of 6.5, a pH value that is achieved regularly in various brain regions during ischemia and hypoxia (22), with the hippocampus affected the most (23). Acidic brain pH values have also been reported in cases of AD (24).…”

Section: Discussionmentioning

confidence: 99%

Regulation of serine protease activity by aluminum: implications for Alzheimer disease.

Clauberg

Joshi

1993

Proc. Natl. Acad. Sci. U.S.A.

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The brain of Alzheimer disease patients contains plaques that are diagnostic for the disease. The plaques also contain (-amyloid peptide, a1-antichymotrypsin, and the element aluminum. We present indirect evidence that can relate all three components of plaques to each other in such a way as to suggest their involvement in the etiology of the disease. The P-amyloid peptide is derived by proteolytic processing from 3-amyloid precursor proteins and some of these proteins contain a domain that is highly homologous to bovine pancreatic trypsin inhibitor. Bovine pancreatic trypsin inhibitor also inhibits a-chymotrypsin and we show that aluminum affects both the activity and the inhibition ofthis enzyme. At pH 6.5, in the presence of aluminum, the enzyme activity is doubled, and the inhibitor is only 1% as effective as in the absence of the metal ion. The inhibition by BX-9, a protease inhibitor prepared from protein components of amyloid plaques, is also reduced by aluminum; so too is that by ar-antichymotrypsin but to a lesser degree. In the Alzheimer brain, we propose that aluminum may accelerate proteolytic processing of the P-amyloid precursor protein by suppression of the inhibitor domain. Thus, the 8-amyloid peptide may accumulate and initiate plaque formation.Increased levels of aluminum have been observed in neuritic deposits, the plaques and the neurofibrillary tangles, of Alzheimer disease (AD) (1) and amyotrophic lateral sclerosis (2). Several in vitro studies have demonstrated the neurotoxicity of aluminum (3). Recent epidemiological evidence associates increased bioavailability ofaluminum with incidence of AD (4). Because the solution chemistries of aluminum and iron are very similar (5), the observed slow accumulation of aluminum in brain and bone tissue is suggested to occur via the iron transport and storage systems (3). Despite the in vivo and in vitro evidence, no initial event(s) for the involvement of aluminum in AD or amyotrophic lateral sclerosis has been established. Therefore, some researchers have questioned (35) the importance or the role of aluminum in the early pathogenesis of these neurological disorders.By contrast, the /3-amyloid peptide found at the "heart" of AD plaques remains a consistent feature ofAD (6, 7). Recent discoveries of B-amyloid mutations in some cases of earlyonset familial AD further underscore the importance of 3-amyloid peptide in the etiology of AD (8). The P-amyloid peptide(s) has 39-43 amino acids and is part of the family of 3-amyloid precursor proteins that contain 695, 751, and 770 amino acids that upon proteolysis generate the 83-amyloid peptide(s). The two larger precursors (751 and 770 amino acids long) also contain a 56-amino acid segment whose sequence is >60% homologous to the bovine pancreatic trypsin inhibitor (bPJI). This discovery suggested the possible role ofthe inhibitor segment in regulating the proteolytic processing of the precursor proteins to generate f3-amyloid peptide(s). However, the pool of f3-amyloid protein precursors is neither ...

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Lactate and pH in the Brain: Association and Dissociation in Different Pathophysiological States

Cited by 172 publications

References 45 publications

Biochemical and molecular studies using human autopsy brain tissue

Biochemical and molecular studies using human autopsy brain tissue

Experimental Biology of Cerebral Hypoxia-Ischemia: Relation to Perinatal Brain Damage

Regulation of serine protease activity by aluminum: implications for Alzheimer disease.

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