Biomedical subjects

T A Cadoux-Hudson

Publications and source records attributed to T A Cadoux-Hudson.

At least 19 recordsLinked to original sources

PubMed2001

In vitro therapy with dobutamine, isoprenaline and sodium nitroprusside protects vascular smooth muscle metabolism from subarachnoid haemorrhage induced cerebral vasospasm.

BACKGROUND: The cerebrospinal fluid (CSF) from subarachnoid haemorrhage (SAH) patients with cerebral vasospasm stimulates vasoconstriction and oxygen consumption in the porcine carotid artery in vitro. Stimulation of oxygen consumption has been used as an in vitro model of vasospasm to assess the relative benefits of nimodipine, isoprenaline, dobutamine, and sodium nitroprusside (SNP). METHOD: Samples of human CSF were obtained from SAH patients and applied to de-endothelialised porcine carotid artery. Stimulation of oxygen consumption (as an in vitro marker for a stimulation of the vessels) was monitored and the effects of SNP, isoprenaline, dobutamine or nimodipine were measured. FINDINGS: The CSF from SAH patients with evidence of vasospasm stimulated oxygen consumption to 0.91 +/- 0.17 (microM O2/min/g dry wt, +/- SD p < or = 0.01) and CSF from SAH patients without vasospasm did not significantly stimulate oxygen consumption 0.27 +/- 0.02, with 0.23 +/- 0.03 (microM O2/min/g dry wt) being an unstimulated rate of respiration for the porcine carotid artery. SNP, isoprenaline or dobutamine significantly (p < or = 0.01) decreased the stimulation of oxygen consumption of the porcine carotid artery whereas nimodipine did not. In a cohort of 41 SAH patients who received nimodipine alone or nimodipine and dobutamine, the in hospital mortality rate of the patients who received only nimodipine was 42% as compared to an in hospital mortality rate of 17% in the nimodipine plus dobutamine group P < or = 0.076). INTERPRETATION: The in vivo data on the 41 patients is not statistically significant, so further studies are required to determine if the differences are important. SNP, isoprenaline and dobutamine significantly decreased oxygen consumption of the porcine carotid arteries exposed to CSF from SAH patients who had vasospasm whereas nimodipine did not. Our in vitro results suggest that these compounds require further study in patients with SAH who are at risk for vasospasm because they may have a direct benefit for the vasospastic arteries.

Adrenergic beta-Agonists↗

PubMed2001

Cerebrospinal fluid from subarachnoid haemorrhage patients causes excessive oxidative metabolism compared to vascular smooth muscle force generation.

Cerebrospinal fluid (CSF) from subarachnoid haemorrhage (SAH) patients can stimulate vascular smooth muscle to generate force in vitro. CSF from SAH patients suffering from delayed ischaemic neurological deficits due to cerebral vasospasm can generate near maximal force in vitro and previous experiments have ascribed this generation of force to be a calcium mediated event. The intracellular calcium concentration has been demonstrated to rise during the vasospastic process. Calcium also stimulates oxidative metabolism as does adenosine diphosphate (ADP), the product of adenosine triphosphate (ATP) hydrolysis. Significant alteration in high energy metabolites such as ATP, ADP and phosphocreatine have also been demonstrated in various models of SAH mediated vasospasm. Vascular smooth muscle predominantly uses oxidative metabolism for force generation and reserves glycolytic metabolism for ion homeostasis. A decrease in oxidative metabolism during force generation would imply failing mitochondria and increased glycolytic high-energy phosphate supply. Increased oxidative metabolism would imply a decreased efficiency of the contractile apparatus or mitochondria. The aim of this study was to see if SAH CSF stimulation of porcine carotid artery oxidative metabolism was altered during force generation when compared with incremental calcium stimulation with potassium chloride depolarisation. CSF from patients (n = 10) who had subarachnoid haemorrhage stimulated force generation but with a significant 'right shift' in oxygen consumption. This 'right shift' is indicative of an increased energy cost for contractile work. These results suggest that vascular smooth muscle contractile apparatus, when stimulated by subarachnoid cerebrospinal fluid, is consuming excess adenosine triphosphate during force generation.

Adult↗

PubMed2001

The stimulation of vascular smooth muscle oxidative metabolism by CSF from subarachnoid haemorrhage patients increases with Fisher and WFNS grades.

The purpose of this paper is to present an in vitro method for examining cerebral vasospasm after subarachnoid haemorrhage (SAH) which correlates to the patients' condition. The O2 consumption of the porcine carotid artery was monitored, using an oxygen electrode, after exposure to cerebrospinal fluid (CSF) from patients who had a SAH. The vessels were exposed to CSF from SAH patients at a 1 in 30 dilution. Force measurements were carried out using freeze-dried CSF, reconstituted in the organ bath equivalent to undiluted CSF. These observations were then compared to the patients' condition. We divided the patient CSF samples into those that stimulated oxygen consumption above 0.4 microM/min/g dry wt, and those that did not. It was found that there was a correlation between the stimulation of oxygen consumption and the Fisher grade as well as the World Federation of Neurosurgeons Grading System (WFNS) for the patients. Of the CSF tested, 24 stimulated oxygen consumption above our cut off, and 8 did not (0.84 +/- 0.34, n = 24 compared with the rate of 0.27 +/- 0.1 mumol/min/g dry wt, respectively; SD n = 8) at 180 minutes. We then examined the Fisher Grades of these two groups, the results were 3.21 +/- 0.88 vs 2.25 +/- 0.83 respectively (SD p < or = 0.01). When examining the WFNS System we found a similar difference between the groups that stimulated respiration and those who did not (WFNS Grades of 2.64 +/- 1.1 vs. 1.43 +/- 0.53; p < or = 0.01). The observed stimulation of oxygen consumption also correlated with tension generation in vitro. The CSF from subarachnoid haemorrhage patients stimulates the oxygen consumption of the porcine carotid artery. This stimulation correlated to the WFNS and Fisher Grades of the patients and can be performed using 1:30 dilution of CSF. We conclude that the metabolic changes that occur in the vessels during vasospasm are important parameters for assessing cerebral vasospasm.

Animals↗

PubMed2001

Magnesium protection against in vitro cerebral vasospasm after subarachnoid haemorrhage.

Mg2+ has recently been proposed for the treatment of cerebral vasospasm and is known to dilate vessels. In this study, we examine the effects of Mg2+ on in vitro vasospasm using CSF from vasospastic subarachnoid haemorrhage patients with vasospasm (CSFv). Oxygen consumption and isometric force measurements in the porcine carotid artery were used to assess the contractile and metabolic status of the vessels' responses to CSFv and the effect of Mg2+. Mg2+ caused a dose dependant decrease in tension following contraction by CSFv. Mg2+ (12 mM) caused a normalization of relaxation rate in tissue exposed to CSFv, caused a significant decrease in basal oxygen consumption, as well as significantly decreasing the rate of oxygen consumption of the porcine carotid artery when stimulated by CSF (0.70 +/- 0.12 versus. 0.46 +/- 0.1 micromol O2 min(-1) g(-1)). Acute Mg2+ addition demonstrated the most effective protection using an assay based on CSFv contraction. These results suggest that Mg2+ can protect vascular smooth muscle exposed to CSFv by benefiting contractile behaviour and metabolism of the arteries.

Animals↗

PubMed2001

Altered cellular metabolism following traumatic brain injury: a magnetic resonance spectroscopy study.

Experimental studies have reported early reductions in pH, phosphocreatine, and free intracellular magnesium following traumatic brain injury using phosphorus magnetic resonance spectroscopy. Paradoxically, in clinical studies there is some evidence for an increase in the pH in the subacute stage following traumatic brain injury. We therefore performed phosphorus magnetic resonance spectroscopy on seven patients in the subacute stage (mean 9 days postinjury) following traumatic brain injury to assess cellular metabolism. In areas of normal-appearing white matter, the pH was significantly alkaline (patients 7.09 +/- 0.04 [mean +/- SD], controls 7.01 +/- 0.04, p = 0.008), the phosphocreatine to inorganic phosphate ratio (PCr/Pi) was significantly increased (patients 4.03 +/- 1.18, controls 2.64 +/- 0.71, p = 0.03), the inorganic phosphate to adenosine triphosphate ratio (Pi/ATP) was significantly reduced (patients 0.37 +/- 0.10, controls 0.56 +/- 0.19, p = 0.04), and the PCr/ATP ratio was nonsignificantly increased (patients 1.53 +/- 0.29, controls 1.34 +/- 0.19, p = 0.14) in patients compared to controls. Furthermore, the calculated free intracellular magnesium was significantly increased in the patients compared to the controls (patients 0.33 +/- 0.09 mM, controls 0.22 +/- 0.09 mM, p = 0.03)). Proton spectra, acquired from similar regions showed a significant reduction in N-acetylaspartate (patients 9.64 +/- 2.49 units, controls 12.84 +/- 2.35 units, p = 0.03) and a significant increase in choline compounds (patients 7.96 +/- 1.02, controls 6.67 +/- 1.01 units, p = 0.03). No lactate was visible in any patient or control spectrum. The alterations in metabolism observed in these patients could not be explained by ongoing ischemia but might be secondary to a loss of normal cellular homeostasis or a relative alteration in the cellular population, in particular an increase in the glial cell density, in these regions.

Adenosine Triphosphate↗

PubMed2001

Abnormal cerebral blood volume in regions of contused and normal appearing brain following traumatic brain injury using perfusion magnetic resonance imaging.

Following traumatic brain injury, there may be secondary alterations in cerebrovascular parameters leading to ischemia and further cellular damage. To assess possible subacute hemodynamic disturbances following traumatic brain injury, we used conventional and perfusion magnetic resonance imaging (MRI) in 18 patients, on average 10 days following injury. Six of the 18 patients had focal contusions or edema visible on conventional MRI. These six patients had a significantly reduced normalized regional cerebral blood volume (rCBV) in the regions of focal pathology compared to equivalent areas in control subjects (patients 0.47 +/- 0.20 [means +/- SD], controls 1.02 +/- 0.11, p < 0.001). In addition, four of these six patients had an increased rCBV (outside control range) in the region of normal appearing brain immediately surrounding the contusion. These six patients were more significantly injured and had a worse clinical outcome compared to the remaining patients (p = 0.004,p = 0.03, respectively). There were five patients who had a region of reduced rCBV (outside control range) in a quadrant of normal appearing white matter, away from any visible abnormality, who were not more significantly injured than the remaining patients but went on to have a significantly poorer clinical outcome (p = 0.27, p = 0.01, respectively). Traumatic brain injury is a heterogeneous insult causing a variety of pathology, not all of which is visible using conventional imaging methods. The current study has shown that regions of both normal appearing and contused brain may have an abnormal rCBV and that alterations in rCBV may play a role in determining the clinical outcome of patients.

Adult↗

PubMed2001

How useful is magnetic resonance imaging in predicting severity and outcome in traumatic brain injury?

Major advances have been made in the ever-expanding field of magnetic resonance imaging and related technologies, such as magnetic resonance spectroscopy, haemodynamic and functional imaging. Although these magnetic resonance modalities are of great research interest, it is still questionable as to how useful these investigations are in the clinical setting. All of these modalities strive to define a few variables that might dominate the heterogeneous but common aetiopathology of traumatic brain injury. Recent studies have found that the use of various magnetic resonance imaging techniques at early and delayed time points can provide useful information with regard to the severity and clinical outcome of patients following traumatic brain injury. These new observations offer opportunities for improved clinical management in such patients.

Brain Damage, Chronic↗

PubMed2000

The presence of an extractable substance in the CSF of humans with cerebral vasospasm after subarachnoid haemorrhage that correlates with phosphatase inhibition.

The cellular events leading to cerebral vasospasm after subarachnoid haemorrhage are poorly understood, although an increase in smooth muscle myosin light chain phosphorylation has been observed. This study set out to determine if phosphatase inhibition may be involved in the pathological maintenance of tension observed during vasospasm. We found that 1 nM okadaic acid, a type 2A protein phosphatase inhibitor, elicited an increase in rate of O(2) consumption in the porcine carotid artery similar to that by cerebrospinal fluid (CSF) from vasospastic patients (CSF(V), n=5) (control 0.23+/-0.03, CSF(V) 0.84+/-0.16 and okadaic acid 0.85+/-0.02 micromol min(-1) g dwt(-1)). It was also observed that phosphatase inhibition with 1 nM okadaic acid significantly slowed relaxation after a stretch in a similar fashion to CSF(V) haemorrhage. CSF from vasospastic subarachnoid haemorrhage patients, but not from those without vasospasm, contains an extractable substance which modulates myosin light chain phosphorylation in vitro. A phosphatase preparation obtained from the porcine carotid artery dephosphorylated 63+/-2% of the phosphorylated (MLC(20)) substrate in vitro, and non-vasospastic CSF treated enzyme dephosphorylated 60+/-2.6%. Okadaic acid inhibited phosphatase dephosphorylated only 7.5+/-1% of the substrate where CSF(V) treated enzyme dephosphorylated 22+/-2.8% of the substrate. We conclude that inhibition of smooth muscle phosphatase may be involved in the mechanisms associated with cerebral vasospasm after subarachnoid haemorrhage.

Animals↗

PubMed2000

Leptomeningeal glioblastoma presenting with multiple cranial neuropathies and confusion.

Glioblastoma multiforme (GBM) is the commonest primary malignant neoplasm of the CNS. Usually, patients present with seizures and headache but in the elderly, confusion and generalised cognitive decline are more frequently the initial features. Multiple cranial nerve lesions as a manifestation of leptomeningeal meningitis is a rare presentation of GBM. The diagnosis is not often suggestive on either brain computed tomography (CT) or magnetic resonance imaging (MRI) and is usually confirmed by cerebrospinal fluid (CSF) cytology or histology. We describe the case of an 80-year-old man, who presented with multiple cranial nerve palsies and confusion secondary to leptomeningeal gliomatosis, in whom GBM was detected along the intra-ventricular lining of the left lateral ventricle at ventriculoscopy, in the absence of a distinct parenchymal lesion.

Age Factors↗

PubMed2000

Oxidative degradation of bilirubin produces vasoactive compounds.

Subarachnoid haemorrhage is often followed by haemolysis and concomitant oxidative stress, and is frequently complicated by pathological vasoconstriction or cerebral vasospasm. It is known that upregulation of haem oxygenase (HO-1) is induced by oxidative stress and results in release of biliverdin and bilirubin (BR), which are scavengers of reactive oxygen species (ROS). Here we report biomimetic studies aimed at modelling pathological conditions leading to oxidative degradation of BR. Oxidative degradation products of BR, formed by reaction with hydrogen peroxide (an ROS model system), demonstrated biological activity by stimulating oxygen consumption and force development in vascular smooth muscle from porcine carotid artery. Analogous biological activity was observed with vasoactive cerebrospinal fluid from subarachnoid haemorrhage patients. Three degradation products of BR were isolated: two were assigned as isomeric monopyrrole (C9H11N2O2) derivatives, 4-methyl-5-oxo-3-vinyl-(1, 5-dihydropyrrol-2-ylidene)acetamide and 3-methyl-5-oxo-4-vinyl-(1, 5-dihydropyrrol-2-ylidene)acetamide and the third was 4-methyl-3-vinylmaleimide (MVM), a previously isolated photodegradation product of biliverdin. Possible mechanisms of oxidative degradation of BR are discussed. Tentative assignment of these structures in the cerebrospinal fluid (CSF) of cerebral vasospasm patients has been made. It is proposed that one or more of the degradation products of biliverdin or bilirubin are involved in complications such as vasospasm and or pathological vasoconstriction associated with haemorrhage.

Bilirubin↗

PubMed2000

Early proton magnetic resonance spectroscopy in normal-appearing brain correlates with outcome in patients following traumatic brain injury.

The long-term clinical outcome following traumatic brain injury (TBI) can be difficult to predict. Proton magnetic resonance spectroscopy (MRS) has previously been used to demonstrate abnormalities in regions of white matter that appear normal on conventional imaging in patients following TBI. We report MRI and MRS studies of 26 patients performed at an early time point following injury (mean 12 days, n = 21) and at a later time point (mean 6.2 months, n = 15). The proton MRS was acquired from the posterior part of a normal-appearing frontal lobe containing predominantly white matter using stimulated echo acquisition mode to localize, with a relaxation time of 3000 ms and echo time of 30 ms. At both the early and late time points the N:-acetylaspartate/creatine ratio (NAA/Cr) was significantly reduced (P = 0.03, P = 0.005, respectively), the choline/creatine ratio (Cho/Cr) significantly increased (P = 0.001, P = 0.004, respectively) and the myo-inositol/creatine ratio (Ins/Cr) significantly increased (P = 0.03, P = 0.03, respectively) compared with controls. There was a small, but significant, further reduction (P = 0.02) in the NAA/Cr between the two studies in the 10 patients for whom data was available, at both time points. The NAA/Cr acquired at the early time point significantly correlated with the clinical outcome of the patients, assessed using either the Glasgow outcome scale (P = 0.005, n = 17) or the disability rating scale (P < 0.001, n = 17). We conclude that there is a sustained alteration in NAA and Cho. These findings provide possible evidence for cellular injury (NAA loss reflecting neuroaxonal cell damage and raised Cho and Ins reflecting glial proliferation) not visible by conventional imaging techniques. This may be relevant to understanding the extent of disability following TBI.

Adolescent↗

PubMed2000

Evidence for cellular damage in normal-appearing white matter correlates with injury severity in patients following traumatic brain injury: A magnetic resonance spectroscopy study.

Neuropsychological studies in patients who have suffered traumatic brain injury show that the eventual clinical outcome is frequently worse than might be predicted from using conventional (CT or T(1)/T(2)-weighted MRI) imaging. Furthermore, patients who have sustained an initial mild or moderate injury may show long-term disability. This implies that there may be abnormalities in areas of the brain that actually appear normal on conventional imaging. Proton magnetic resonance spectroscopy studies have shown that N-acetylaspartate and choline-containing compounds can provide measures of cellular injury. We report MRI and proton magnetic resonance spectroscopy studies of 19 head-injured patients performed once the patients were clinically stable (mean 11 days after injury, range 3-38 days). Proton magnetic resonance spectra were acquired from frontal white matter that on conventional MRI appeared normal. The brain N-acetylaspartate/creatine ratio was reduced [patients (mean +/- standard deviation), 1.28 +/- 0.25; controls, 1.47 +/- 0. 24; P = 0.04] and the choline/creatine ratio was increased (patients, 0.85 +/- 0.18; controls, 0.63 +/- 0.10; P < 0.001) compared with controls. When the severity of the injury was assessed using either the Glasgow coma scale or the length of post-traumatic amnesia, the increase in the choline/creatine ratio was significant even in the mildly injured group (P = 0.008 and P = 0.04, respectively). Furthermore, there was a significant correlation (P = 0.008) between the severity of head injury and the N-acetylaspartate/choline ratio. We conclude that there is an early reduction in N-acetylaspartate and an increase in choline compounds in normal-appearing white matter which correlate with head injury severity, and that this may provide a pathological basis for the long-term neurological disability that is seen in these patients.

Adolescent↗

PubMed1999

Normal pressure hydrocephalus: developments in determining surgical prognosis.

Research into normal pressure hydrocephalus has often focused on the clinical dilemma of selecting patients who will benefit from cerebrospinal fluid diversion. Recent developments in imaging and lumbar infusion tests are throwing light on the underlying pathophysiology, providing researchers with new avenues for the development of reliable investigative tools.

Humans↗

PubMed1998

Role of ischaemia in the genesis of oedema surrounding meningiomas assessed using magnetic resonance imaging and spectroscopy.

Oedema surrounding meningiomas is well known, but its pathogenesis remains obscure. Perfusion and metabolism in this peritumoural parenchyma were studied preoperatively in eight patients using magnetic resonance imaging, dynamic perfusion scanning and proton spectroscopy. Relative cerebral blood volumes (CBV) and metabolite ratios were calculated for the tumour and peritumoural brain. All meningiomas showed gadolinium enhancement, high choline (Ch), low creatine (Cr) and low N-acetyl aspartate (NAA) [Ch: (Ch + Cr) 0.67, SD 0.13, NAA: (Ch + Cr) 0.18, SD 0.15]. Lactate was present in four tumours [lactate: (Ch + Cr) 0.32, SD 0.27]. Extremely low gadolinium passage and low CBV were seen in the 2 cm peritumoural region, with elevated lactate [lactate: (Ch + Cr) 0.26, SD 0.18]. Four centimetres from tumour margin the CBV was still reduced (65, SD 20% with less lactate [lactate: (Ch + Cr) 0.12, SD 0.01]. Relative CBV is reduced around meningiomas and is associated with lactate, suggesting that oligaemia and altered metabolism may be part of the pathology in peritumoural oedema. Such changes may be important in determining functional recovery after surgery.

Adult↗

PubMed1991

Effect of insulin on intracellular pH and phosphate metabolism in human skeletal muscle in vivo.

1. 31P nuclear magnetic resonance spectroscopy and the hyperinsulinaemic-euglycaemic clamp were used simultaneously to assess the effect of insulin on intracellular pH and the major phosphorus-containing metabolites of normal human skeletal muscle in vivo in four normal subjects. 2. Insulin and glucose were infused for 120 min. Plasma insulin increased approximately 10-fold over preclamp levels (5.6 +/- 0.9 m-units/l pre-clamp and 54 +/- 5 m-units/l over the last hour of infusion; mean +/- SEM, n = 4). Plasma glucose concentration did not change significantly (5.4 +/- 0.2 mmol/l pre-clamp and 5.5 +/- 0.1 mmol/l over the last hour of infusion). 3. Insulin and glucose infusion resulted in a decline in the intracellular pH of forearm muscle of 0.027 +/- 0.007 unit/h (P less than 0.01), whereas in control studies of the same subjects, pH rose by 0.046 +/- 0.005 unit/h (P less than 0.001). 4. In the clamp studies, intracellular inorganic phosphate concentration rose by 18%/h, whereas ATP, phosphocreatine and phosphomonoester concentrations did not change. In plasma, inorganic phosphate concentration was 1.16 +/- 0.05 mmol/l before infusion, and this decreased by a mean rate of 0.14 mmol h-1 l-1. No change was observed in any of these intracellular metabolites in the control studies. 5. The results show that, under physiological conditions, insulin does not raise intracellular pH in human muscle, and thus cannot influence muscle metabolism by this mechanism. The results also suggest that insulin causes a primary increase in the next flux of inorganic phosphate across the muscle cell membrane.

Adult↗

PubMed1991

Biochemical changes within a multiple sclerosis plaque in vivo.

Magnetic resonance spectroscopy (MRS) was performed on a superficial part of the brain containing a large multiple sclerosis (MS) lesion. Reduced levels of phosphocreatine (PCr) relative to adenosine triphosphate (ATP) were found suggesting an abnormality in energy metabolism, with an increase in the phosphodiester (PDE) peak. A follow up study 16 months later revealed reduction in size of the lesion on MRI and normal intracellular biochemistry by MRS. Four MS patients without visible superficial cerebral lesions showed no significant changes in phosphorus metabolism.

Adenosine Triphosphate↗

PubMed1990

Persistent metabolic sequelae of severe head injury in humans in vivo.

Six patients who had suffered severe non-penetrating high velocity head injuries were investigated with phosphorus (31P) magnetic resonance spectroscopy (MRS) to determine, non-invasively, long-term alteration in intracellular biochemistry. The normal subjects were found to have a constant intracellular pH (pHi, 7.03 +/- 0.03) with depth into the brain. The adenosine triphosphate (ATP, 3.46 +/- 0.66 mmol/L of brain tissue), inorganic phosphate (Pi, 1.15 +/- 0.41 mmol/L) and phosphomonester (PME, 2.76 +/- 1.0 mmol/L) tissue concentrations did not alter significantly with depth into normal brain. The phosphocreatine (PCr, 2 cm = 5.21 +/- 1.25, 5 cm = 4.85 +/- 1.49 mmol/L) was slightly reduced, whilst phosphodiesters (PDE, 2 cm = 9.53 +/- 2.6, 5 cm = 14.41 +/- 4.2 mmol/L) rose significantly between tissue comprising mainly of gray (2 cm) and white matter (5 cm). In comparison the contra-lateral hemisphere to the side of worst spasticity showed significant changes a considerable time after injury (6-18 months). The intracellular metabolite tissue concentrations were all reduced by 30% (ATP 2.53 +/- 1.0 mmol/L, PCr 3.44 +/- 0.8 mmol/L) with PDE reduced most significantly at depth (5 cm = 8.4 +/- 3.4 mmol/L), compatible with the cerebral atrophy seen in these patients. In white matter the pHi also decreased with depth (2 cm = 7.03 +/- 0.03, 5 cm = 6.89 +/- 0.05). The reduction in pHi so long after injury is difficult to explain in these steady-state conditions. A structural abnormality, such as a disorder in the blood brain barrier or accumulation of large acidic lysosomes, could cause these pHi changes. There may also be a failure in blood flow regulation, with near critical fluctuations in blood flow both with time and space.

Accidents, Traffic↗

PubMed1990

Response of the human brain to a hypercapnic acid load in vivo.

1. The aim of this investigation was to measure the change in intracellular pH of human brain in vivo in response to hypercapnia. 2. Five healthy male subjects inspired air for 20 min and then 5% CO2/95% O2 for 30 min, of which the first 10 min was used to achieve a steady-state end-tidal CO2 measurement. 3. 31P nuclear magnetic resonance spectroscopy was used to measure intracellular pH while breathing air and during hypercapnia. Simultaneous localization between superficial and deep brain was achieved by using the phase-modulated rotating frame imaging technique. One subject volunteered to breath air for a further phase-modulated rotating frame imaging study while recovering from hypercapnia. 4. End-tidal CO2 increased when breathing 5% CO2/95% O2 (on air, 5.57 +/- 0.21%; on 5% CO2/95% O2, 6.41 +/- 0.16%; rise = +0.84 +/- 0.09%; means +/- SEM) causing a reduction in brain intracellular pH, which was more pronounced in deep brain (5 cm = mainly white matter, from 7.02 +/- 0.006 pH units to 6.96 +/- 0.001 pH units, mean +/- SEM) than in superficial brain (2 cm = mainly grey matter, from 7.02 +/- 0.006 pH units to 7.00 +/- 0.006 pH units, mean +/- SEM). 5. The white matter responded to hypercapnia with a greater fall in intracellular pH than the grey matter. This could either be due to differences in blood flow between grey and white matter in response to hypercapnia or to differences in intracellular pH regulation/buffering between these two tissues.

Brain↗