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B R Ransom

Publications and source records attributed to B R Ransom.

At least 55 records · Page 3Linked to original sources
PubMed1994

Sodium channel mRNAs in cultured spinal cord astrocytes: in situ hybridization in identified cell types.

The expression of rat brain sodium channel alpha-subunit mRNAs I, II and III and a putative glial cell-specific sodium channel (NaG) mRNA was examined in cultured astrocytes from P-0 rat spinal cord by RNA blot hybridization and by non-isotope in situ hybridization cytochemistry utilizing two independent sets of isoform-specific RNA probes. Sodium channel mRNA I was not detectable in the cultured astrocytes by RNA blot or in situ hybridization. Sodium channel mRNA II showed negligible-to-low levels of expression in flat, fibroblast-like and 'pancake' astrocytes at 4 days in vitro (div), while stellate, process-bearing astrocytes exhibited low-to-moderate levels of mRNA II expression. At 7 div, mRNA II expression ranged from low-to-moderate in flat astrocytes and was moderately high in most process-bearing astrocytes. In RNA blots, a weak band was observed at 9.5 kb. Sodium channel mRNA III expression was negligible in flat astrocytes and was detectable in low-to moderate levels in stellate astrocytes beginning at 4 div; by 7 div, mRNA III was detectable in low levels in flat astrocytes and low-to-moderate levels in stellate astrocytes. RNA blots showed two bands of nearly equal intensity, one at 9.0 kb and one at 7.2 kb. NaG mRNA showed increased expression with time in culture, being detectable in flat and stellate astrocytes at 4 div and becoming very prominent in flat astrocytes at extended times in culture. In RNA blots of cultured astrocytes at 7 div, a strong hybridizing signal with the NaG probe was observed. These observations demonstrate that flat and stellate astrocytes cultured from rat spinal cord express rat brain sodium channel mRNA II and III, and NaG, and suggest that astrocytes in vitro may co-express multiple forms of sodium channel mRNA.

Animals↗
PubMed1994

Rat hippocampal astrocytes exhibit electrogenic sodium-bicarbonate co-transport.

1. We probed for the expression of electrogenic Na+/HCO3- co-transport in cultured mammalian astrocytes by recording voltage and current changes induced by bath application of HCO3-, with the use of patch-clamp electrophysiology. Application of 25 mM HCO3-, at a constant pHo, to astrocytes bathed in a nominally HCO3(-)-free solution, produced an abrupt and reversible change in membrane potential ranging from +3 to -30 mV [-11.8 +/- 9.34 (SD) mV]; 55% of cells showed relatively large hyperpolarizing responses (-18.8 +/- 6.23 mV), whereas 45% showed only small shifts in membrane potential (range of -5 to +3 mV; -1.9 +/- 1.96 mV). 2. The size of the HCO3(-)-induced hyperpolarization was strongly related to the cell's initial resting membrane potential in HCO3(-)-free solution; the larger responses were seen in cells with relatively low resting membrane potentials (-48.5 +/- 9.4 mV), and the smaller responses were seen in cells with more negative potentials (-68.1 +/- 6.5 mV). The membrane potentials of hippocampal astrocytes were highly variable in HCO3(-)-free solution (range -38 to -80 mV; -60.9 +/- 12.53); this variability was greatly reduced in HCO3(-)-containing solution (range -59 to -82 mV; -68.5 +/- 4.8). 3. The magnitude of the HCO3(-)-induced response was less strongly correlated with cell input resistance, which was higher in the larger responder cells than in the small responders. However, the differences in input resistance were insufficient to account for the different HCO3(-)-induced responses observed. 4. In the presence of extracellular Ba2+, which by blocking K+ conductance depolarized cells by 30-50 mV, cells that initially showed a small response, showed a large and completely reversible hyperpolarization (-18.4 +/- 6.13 mV) to application of 25 mM HCO3-. In Na(+)-free solution, the HCO3(-)-induced hyperpolarization was reduced by 66%, and the response was not sustained, as in Na(+)-containing solution. Removal of extracellular Cl- had no effect on the HCO3- response The stilbene derivative 4,4'-diisothiocyano-2,2'-stilbene disulfonate (DIDS), a blocker of anion transport, eliminated the HCO3(-)-induced hyperpolarization. Blockers of Na+/K+ ATPase and Na(+)-H+ exchange were without effect. These observations indicated the presence of an electrogenic Na+/HCO3- co-transporter in hippocampal astrocytes. 6. Voltage-clamp recording demonstrated that the HCO3(-)-induced hyperpolarization was caused by outward currents averaging 335 +/- 104 pA. The reversal potential of the HCO3(-)-induced current ranged between -80 and -99 mV with an average = -86.1 +/- 6.2 mV.(ABSTRACT TRUNCATED AT 400 WORDS)

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1994

Modulation of anoxic injury in CNS white matter by adenosine and interaction between adenosine and GABA.

1. We examined the role of adenosine in the development of anoxic injury in a CNS white matter tract, the rat optic nerve. Application of adenosine protected the rat optic nerve from anoxic injury; 2.5 microM adenosine increased compound action potential (CAP) recovery after a standard 60-min anoxic period from 28.6 +/- 2.5%, mean +/- SE, to 51.0 +/- 3.1% (P < 0001). The protective effect of adenosine was abolished by the adenosine receptor antagonist theophylline (100 microM). 2. The protective effect of adenosine evolved slowly after adenosine application; maximum protection required 60 min of adenosine exposure before the onset of anoxia. The concentration dependence of the protective effect was parabolic, with maximum protection at 2.5 microM. Neither high nor very low adenosine concentrations protected against anoxia. These characteristics are similar to those previously found for the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the same preparation. 3. Inhibition of adenosine receptors (100 microM theophylline) reduced the level of recovery from that found under control conditions (24.3 +/- 4.8% compared with 36.2 +/- 2.5%, P < 0.05). The adenosine uptake inhibitor propentofylline, which potentiates release of endogenous adenosine during brain anoxia, significantly increased CAP recovery after anoxia. This effect was abolished by theophylline. It appeared therefore that release of endogenous adenosine limited injury in the optic nerve during anoxia. 4. The protective effect of adenosine was removed by pretreatment with the protein kinase C (PKC) inhibitor staurosporine (10 nM), indicating that activation of PKC was required for protection after exposure to adenosine.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1994

Depolarization-induced alkalinization (DIA) in rat hippocampal astrocytes.

1. Depolarization of glial cells causes their intracellular pH (pHi) to increase. To more completely characterize this depolarization-induced alkalinization (DIA) in mammalian astrocytes, we studied DIA in cultured rat hippocampal astrocytes. Astrocytes were loaded with the fluorescent pH indicator 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein (BCECF), and pHi was monitored with the use of an imaging system. Cells were studied approximately 24 h after removing them from serum-containing culture medium. In HCO-3-buffered solution containing 3 mM K+, mean baseline pHi was 7.14 +/- 0.14 (mean +/- SD). 2. Astrocyte pHi rapidly and reversibly alkalinized when bath [K+] was increased from 3 to 12 mM. In HCO-3-buffered solution, mean DIA amplitude was 0.16 +/- 0.01 pH units, and mean rate of pHi change was 0.076 +/- 0.03 pH units/min. In contrast, DIA elicited in nominally HCO-3-free, N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES)-buffered solution was much smaller (0.03 +/- 0.01 pH units, 0.04 +/- 0.01 pH units/min; P < 0.0001), indicating that DIA was, in large part, a HCO-3-dependent process. Subsequent experiments were carried out in HCO-3-buffered solution. 3. The relationship between DIA and variable changes in bath [K+] was examined. Increasing bath [K+] from 3 to 6 mM produced a DIA of 0.07 +/- 0.04 pH units, and lowering [K+] to 0.5 mM resulted in an acid shift of 0.08 +/- 0.05 pH units. The effects of these changes in [K+] on membrane potential were measured in separate experiments by whole cell patch-clamp recording. On the basis of these data, it was possible to construct a relationship between Vm and pHi; shifting membrane potential approximately 10 mV resulted in a pHi shift of approximately 0.07. 4. Application of 0.5 mM Ba2+ depolarized Vm and elicited DIA in astrocytes. This indicated that depolarization, in the absence of an increase in [K+], could cause DIA. Application of Ba2+ also blocked K(+)-induced DIA, presumably because blockade of K+ channels prevented any depolarization by K+. 5. Cells with more alkaline baseline pHis exhibited larger and more rapidly developing DIAs. The mechanism of this effect is not known. 6. The timing of serum removal affected astrocyte DIA. Cells studied approximately 24 h after serum removal always exhibited robust DIA (mean = 0.16 +/- 0.01 pH units).(ABSTRACT TRUNCATED AT 400 WORDS)

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1993

Morphology of astrocytes and oligodendrocytes during development in the intact rat optic nerve.

The detailed three-dimensional morphology of macroglial cells was determined throughout postnatal development in the intact rat optic nerve, a central nervous system white matter tract. Over 750 cells were analyzed by intracellular injection of horseradish peroxidase or Lucifer Yellow to provide a new perspective of glial differentiation in situ. Retrograde analysis of changes in glial morphology allowed us to identify developmental timetables for three morphological subclasses of astrocytes and oligodendrocytes, and to estimate their time of emergence from undifferentiated glial progenitors. Glial progenitors were recognised throughout postnatal development and persisted in 35-day-old nerves, where we suggest they represent adult progenitor cells. Astrocytes were present at birth, but the majority of these cells developed over the first week as three morphological classes emerged having either transverse, random, or longitudinal process orientation. Several lines of evidence led us to believe that the majority of astrocytes in the rat optic nerve were morphological variations of a single cell type. Young oligodendrocytes were first observed 2 days after birth, indicating that they diverged from progenitors at or near this time. During early development these cells extended a large number of fine processes, which then bifurcated and extended along axons. Later, as myelination proceeded, oligodendrocytes exhibited fewer processes which grew symmetrically and uniformly along the axons, resulting in a highly stereotypic mature oligodendrocyte form. Our analysis of oligodendrocyte growth suggests that these cells did not myelinate axons in a random manner and that axons may influence the myelinating processes of nearby oligodendrocytes.

Animals↗
PubMed1993

Noninactivating, tetrodotoxin-sensitive Na+ conductance in rat optic nerve axons.

The ionic current underlying the upstroke of axonal action potentials is carried by rapidly activating, voltage-dependent Na+ channels. Termination of the action potential is mediated in part by the rapid inactivation of these Na+ channels. We previously demonstrated that an influx of Na+ plays a critical role in the cascade leading to irreversible anoxic injury in central nervous system white matter. We speculated that a noninactivating Na+ conductance mediates this pathological Na+ influx and persists at depolarized membrane potentials as seen in anoxic axons. In the present study we measured the resting compound membrane potential of rat optic nerves using a modified "grease-gap" technique. Application of tetrodotoxin (2 microM) to resting nerves ([K+]o = 3 mM) or to nerves depolarized by 15 or 40 mM K+ resulted in hyperpolarizing shifts of membrane potential. We interpret these shifts as evidence for a persistent, noninactivating Na+ conductance. This conductance is present at rest and persists in nerves depolarized sufficiently to abolish classical transient Na+ currents. PK/PNa ratios were estimated at 35.5, 23.2, and 88 in 3 mM, 15 mM, and 40 mM K+, respectively. We suggest that this noninactivating Na+ conductance may provide an inward pathway for Na+ ions, necessary for the operation of Na+, K(+)-ATPase. Under pathological conditions, such as anoxia, this conductance is the likely route of Na+ influx, which causes damaging Ca2+ entry through reverse operation of the Na(+)-Ca2+ exchanger. The presence of this conductance in white matter axons may provide a therapeutic opportunity for diseases such as stroke and spinal cord injury.

Animals↗
PubMed1993

Protection of the axonal cytoskeleton in anoxic optic nerve by decreased extracellular calcium.

Since CNS white matter tracts contain axons, oligodendrocytes and astrocytes but not synapses, it is likely that anoxic injury of white matter is mediated by cellular mechanisms that do not involve synapses. In order to test the hypothesis, that anoxic injury of white matter is mediated by an influx of Ca2+ into the intracellular compartment of axons, we compared the ultrastructure of axons in rat optic nerve exposed to 60 min of anoxia in artificial cerebrospinal fluid (aCSF) containing normal (2 mM) Ca2+, and in aCSF containing zero-Ca2+ together with 5 mM EGTA. Optic nerves fixed at the end of 60 min of anoxia in 2 mM Ca2+ exhibit extensive ultrastructural alterations including disruption of microtubules and neurofilaments within the axonal cytoskeleton, development of membranous profiles and empty spaces between the axon and the ensheathing myelin, and swelling of mitochondria with loss of cristae. Bathing the nerves in zero-Ca2+ aCSF during anoxia protected the axons from cytoskeletal changes; after 60 min of anoxia, optic nerve axons retained normal-appearing microtubules and neurofilaments. Membranous profiles were rare, and empty spaces between axons and myelin did not develop in anoxic optic nerves bathed in zero-Ca2+ aCSF. Disorganization of cristae in axonal mitochondria was observed in anoxic optic nerves even when Ca2+ was omitted from the medium. Because Ca(2+)-mediated injury is known to disrupt the axonal cytoskeleton, these results support the hypothesis that anoxia triggers an abnormal influx of Ca2+ into myelinated axons in CNS white matter.

Animals↗
PubMed1993

Development of cell-cell coupling among cells of the oligodendrocyte lineage.

The development of functional gap-junctional communication was studied in cells of the oligodendrocyte lineage. The presence of cell-cell coupling was determined by the passage of current between cells using a double whole-cell patch-clamp system or by injecting the low molecular weight dye Lucifer yellow into individual cells via a patch pepette and observing the diffusion of the dye into adjacent cells. The developmental stage of the cells under study was determined using antibodies to specific surface markers (04, 01, and 010) that characterize cells of sequential maturity along the oligodendrocyte lineage (Kuhlmann-Krieg et al., 1988; Sommer and Schachner, 1981; 1982). Both stages of precursor cells of this lineage, O4+ and O4-, almost never showed dye or electrical coupling, even though they were in close physical contact with other cells. The O1-positive oligodendrocytes with simple morphology were also noncoupled, with only few exceptions. In contrast, more than 40 percent of more mature, O10-positive oligodendrocytes showed cell-cell coupling detectable with both dye and current injection. Thus, the formation of gap junctions between cells of the oligodendrocyte lineage does not occur with, but some time after, the commitment of the cell to becoming an oligodendrocyte.

Animals↗
PubMed1993

A depolarization-stimulated, bafilomycin-inhibitable H+ pump in hippocampal astrocytes.

Relatively little is known about the mechanisms of pHi regulation in mammalian glial cells. We analyzed pHi regulation in rat hippocampal astrocytes in vitro using the pH-sensitive dye BCECF. All experiments were carried out in CO2/HCO3(-)-free solutions. Recovery from NH4(+)-induced acid loads was strongly dependent on the presence of extracellular Na+ and was inhibited by amiloride and its more specific analog EIPA, indicating the presence of Na(+)-H+ exchange in these cells. Removing bath Na+ or adding amiloride caused resting pHi to shift in the acid direction. Even in the absence of bath Na+ or presence of Na+/H+ inhibitors, however, these astrocytes continued to show significant recovery from acid loads. The mechanism of this amiloride-insensitive and Na(+)-independent pHi recovery process was sought and appeared to be a proton pump. In the absence of Na+, recovery from an acid load was completely blocked by the highly specific blocker of vacuolar-type (v-type) H+ ATPase, bafilomycin A1 (BA1). In normal Na+ containing solutions, exposure to BA1 caused a small acid shift in baseline pHi and slowed recovery rate from NH4(+)-induced acid loads by about 32%. The rate of Na(+)-independent pHi recovery was increased by depolarization with 50 mM [K+] solution, and this effect was rapidly reversible and blocked by BA1. These results indicate that, in CO2/HCO3(-)-free solution, pHi regulation in hippocampal astrocytes was mediated by Na(+)-H+ exchange and by a BA1-inhibitable proton pump. Because the proton pump's activity was influenced by membrane potential, this acid exporting mechanism could contribute to the depolarization-induced alkalinization that is seen in astrocytes. Although v-type H(+)-ATPase had been previously isolated from the brain, this is the first report indicating that it has a role in regulating pHi in brain cells.

Amiloride↗
PubMed1993

Pharmacological protection of CNS white matter during anoxia: actions of phenytoin, carbamazepine and diazepam.

The effects of phenytoin (DPH), carbamazepine (CBZ) and diazepam (DZP) on anoxia-induced injury in CNS white matter were studied using the in vitro rat optic nerve preparation. Optic nerves were subjected to 60 min of anoxia and functional recovery was assessed using the area under the compound action potential. Under normoxic conditions, application of DPH, CBZ and DZP reduced compound action potential area over concentration ranges known to block sodium channels. All three compounds, however, protected against anoxic injury at concentrations below those that inhibited the normoxic compound action potential. Thus, the application of 1 microM DPH, CBZ or DZP during anoxia resulted in compound action potential recovery to 60.0, 53.8 and 69.2% of control, respectively, compared to compound action potential recovery of 34.8% in the absence of drugs (P < .05 in all three cases). In the cases of CBZ and DPH, 60% improvement in recovery from anoxia was produced by concentrations well below those employed clinically to treat epilepsy, suggesting a potential role for these drugs in the protection of CNS white matter from anoxic injury.

Action Potentials↗
PubMed1992

Different Na+ currents in P0- and P7-derived hippocampal astrocytes in vitro: evidence for a switch in Na+ channel expression in vivo.

Hippocampal astrocytes, derived from postnatal day zero (P0) rats, appear to be pluripotential with respect to sodium current expression in vitro, and display Na+ currents with h infinity midpoints close to -65 up to 5 days in vitro (DIV), and Na+ currents with midpoints close to -85 mV at 6 DIV and thereafter. These astrocytes also exhibit a biphasic pattern of Na+ current density, which is expressed at moderate levels at early times in vitro and decreases throughout the first 5 DIV, prior to expressing a second peak for the duration of time in culture. These observations have been interpreted as suggesting that astrocytes in these cultures display a 'switch' in Na+ channel biosynthesis, so that they express different types of Na+ current (with different h infinity curves) at early and later times in culture. To test the hypothesis that a similar switch in Na+ channel expression occurs in vivo, we have used patch-clamp methods to study Na+ current expression in astrocytes derived from rat hippocampus at various stages of postnatal development, P0, P4, P5 and P7. We observed a biphasic distribution of Na+ current density, which was highest in P0- and P7-derived astrocytes (18 pA/pF and 10.3 pA/pF, respectively); astrocytes derived at P4 and P5 did not express sodium currents. While P0-derived astrocytes show depolarized h infinity curves (midpoints close to -65 mV) at early times in culture, P7-derived astrocytes, studied at comparable times in vitro, display hyperpolarized h infinity curves (midpoints close to -85 mV).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Ultrastructural concomitants of anoxic injury and early post-anoxic recovery in rat optic nerve.

To study the effects of anoxia on CNS white matter, we examined the ultrastructure of axons and glial cells in a white matter tract, the rat optic nerve, that was subjected to a standardized anoxic insult in vitro. Previous electrophysiological studies showed that in this model, action potential conduction is rapidly abolished by anoxia, and conduction is restored after reoxygenation in about 30% of axons following a 60-min anoxic period. The present study examined the ultrastructural correlates of anoxic injury and early post-anoxic recovery in this model. Optic nerves examined immediately following 60 min of anoxia displayed numerous large, apparently empty zones located within myelin sheaths adjacent to the axon. The myelin remained compact and retained its periodicity. In some regions, the extracellular space was enlarged. There was mitochondrial swelling with loss of normal cristae. There was also loss of microtubules and, to a smaller degree, of neurofilaments in large-diameter axons. Some nodes of Ranvier in anoxic optic nerves displayed detachment of terminal oligodendroglial loops or retraction of the myelin from the node; the presence of tongue-like processes, extending from nearby cells under the detached myelin loops, suggested a possible role of cell-mediated damage to the paranodal myelin. Bundles of dense astrocyte processes were present, and there was vesicular degeneration of perinodal astrocyte processes. In optic nerves that had been permitted to recover for 60 min in oxygenated Ringers following the anoxic period, empty zones were only rarely observed within myelin sheaths and, when present, were smaller than in optic nerves immediately following 60 min of anoxia. The axoplasm of large fibers continued to show loss of microtubules and neurofilaments, as well as mitochondrial swelling. Myelin appeared normal, and only rare paranodal oligodendroglial processes remained unattached from the axon membrane. These results provide support for the idea that, during anoxia, myelinated axons are damaged with significant injury to cytoskeletal elements, probably due to an influx of calcium. The ultrastructural results, together with our earlier observations on the physiological correlates of anoxia and re-oxygenation, suggest that the development of intramyelinic spaces or damage to paranodes lead to conduction block in the anoxic optic nerve. These results also suggest that repair of these structural abnormalities may provide a morphological basis for the early recovery of conduction that occurs after re-oxygenation.

Animals↗
PubMed1992

Sodium channel expression in optic nerve astrocytes chronically deprived of axonal contact.

Immunocytochemical and electrophysiological methods were used to examine the effect of retinal ablation on the expression of sodium channels within optic nerve astrocytes in situ and in vitro. Enucleation was performed at postnatal day 3 (P3), and electron microscopy of the enucleated optic nerves at P28-P40 revealed complete degeneration of retinal ganglion axons, resulting in optic nerves composed predominantly of astrocytes. In contrast to control (non-enucleated) optic nerve astrocytes, which exhibited distinct sodium channel immunoreactivity following immunostaining with antibody 7493, the astrocytes in enucleated optic nerves did not display sodium channel immunoreactivity in situ. Cultures obtained from enucleated optic nerves consisted principally (greater than 90%) of glial fibrillary acidic protein (GFAP)+/A2B5- ("type-1") astrocytes, as determined by indirect immunofluorescence; GFAP+/A2B5+ ("type-2") astrocytes were not present, nor were GFAP-/A2B5+ (O-2A) progenitor cells. Sodium channel immunoreactivity was not present in GFAP+/A2B5- astrocytes obtained from enucleated optic nerves; in contrast, GFAP+/A2B5- astrocytes from control optic nerves exhibited 7493 immunostaining for the first 4-6 days in culture. Sodium current expression, studied using whole-cell patch-clamp recording, was attenuated in cultured astrocytes derived from enucleated optic nerves. Whereas 39 of 50 type-1 astrocytes cultured from intact optic nerves showed measurable sodium currents at 1-7 days in vitro, sodium currents were present in only 6 of 38 astrocytes cultured from enucleated optic nerves. Mean sodium current densities in astrocytes from the enucleated optic nerves (0.66 +/- 0.3 pA/pF) were significantly smaller than in astrocytes from control optic nerves (7.15 +/- 1.1 pA/pF). The h infinity-curves of sodium currents were similar in A2B5- astrocytes from enucleated and control rat optic nerves. These results suggest that there is neuronal modulation of sodium channel expression in type-1 optic nerve astrocytes, and that, following chronic loss of axonal association in vivo, sodium channel expression is down-regulated in this population of optic nerve astrocytes.

Animals↗
PubMed1992

Effects of temperature on evoked electrical activity and anoxic injury in CNS white matter.

Temperature is known to influence the extent of anoxic/ischemic injury in gray matter of the brain. We tested the hypothesis that small changes in temperature during anoxic exposure could affect the degree of functional injury seen in white matter, using the isolated rat optic nerve, a typical CNS white matter tract (Foster et al., 1982). Functional recovery after anoxia was monitored by quantitative assessment of the compound action potential (CAP) area. Small changes in ambient temperature, within a range of 32 to 42 degrees C, mildly affected the CAP of the optic nerve under normoxic conditions. Reducing the temperature to < 37 degrees C caused a reversible increase in the CAP area and in the latencies of all three CAP peaks; increasing the temperature to > 37 degrees C had opposite effects. Functional recovery of white matter following 60 min of anoxia was strongly influenced by temperature during the period of anoxia. The average recovery of the CAP, relative to control, after 60 min of anoxia administered at 37 degrees C was 35.4 +/- 7%; when the temperature was lowered by 2.5 degrees C (i.e., to 34.5 degrees C) for the period of anoxic exposure, the extent of functional recovery improved to 64.6 +/- 15% (p < 0.00001). Lowering the temperature to 32 degrees C during anoxic exposure for 60 min resulted in even greater functional recovery (100.5 +/- 14% of the control CAP area). Conversely, if temperature was increased to > 37 degrees C during anoxia, the functional outcome worsened, e.g., CAP recovery at 42 degrees C was 8.5 +/- 7% (p < 0.00001). Hypothermia (i.e., 32 degrees C) for 30 min immediately following anoxia at 37 degrees C did not improve the functional outcome. Many processes within the brain are temperature sensitive, including O2 consumption, and it is not clear which of these is most relevant to the observed effects of temperature on recovery of white matter from anoxic injury. Unlike the situation in gray matter, the temperature dependency of anoxic injury cannot be related to reduced release of excitotoxins like glutamate, because neurotransmitters play no role in the pathophysiology of anoxic damage in white matter (Ransom et al., 1990a). It is more likely that temperature affects the rate of ion transport by the Na(+)-Ca2+ exchanger, the transporter responsible for intracellular Ca2+ loading during anoxia in white matter, and/or the rate of some destructive intracellular enzymatic mechanism(s) activated by pathological increases in intracellular Ca2+.

Animals↗