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ABSTRACT: this paper we present some previously published (Gibbs et al., 1977, 1979) findings from pharmaco-behavioural studies, the explanation of which may require the postulation of a role for the glia. The viability of our hypotheses, but not their validity, rests on at least one demonstration that adequate stimuli associated with our learning task give rise to alterations in the ionic state surrounding cells in brain areas shown to be activated specifically during memory processing. We present some recently reported (Sykovfi et al., 1990) and some unpublished data relevant to this issue
10/2002;
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ABSTRACT: Three diffusion parameters of brain tissue, extracellular space volume fraction (alpha), tortuosity (lambda) and non-specific uptake (kappa') of tetramethylammonium were studied in the somatosensory neocortex and subcortical white matter of the rat during postnatal development (postnatal days 2-21) after X-irradiation at postnatal days 0-1. The diffusion parameters were determined from extracellular concentration-time profiles of tetramethylammonium. The tetramethylammonium concentration was measured in vivo with ion-selective microelectrodes positioned 130-200 microns from an iontophoretic source. X-irradiation with a single dose of 40 Gy resulted in typical early morphological changes in the tissue, namely cell death, DNA fragmentation, extensive neuronal loss, blood-brain barrier damage, activated macrophages, astrogliosis, increase in extracellular fibronectin and concomitant changes in all three diffusion parameters. The changes were observed as early as 48 h post-irradiation (at postnatal days 2-3) and still persisted at postnatal day 21. On the other hand, X-irradiation with a single dose of 20 Gy resulted in relatively light neuronal damage and loss, while blood-brain barrier damage, astrogliosis and changes in diffusion parameters were not significantly different from those found with 40 Gy. It is known that the volume fraction of the extracellular space in the non-irradiated cortex is large in newborn rats and diminishes with age [Lehmenkühler A. et al. (1993) Neuroscience 55, 339-351]. X-irradiation with a single dose of 40 or 20 Gy blocked the normal pattern of volume fraction decrease during postnatal development, and in fact brought about a significant increase. At postnatal days 4-5, alpha increased to 0.49 +/- 0.036 in layer III, 0.51 +/- 0.042 in layer IV, 0.48 +/- 0.02 in layer V, 0.48 +/- 0.028 in layer VI and 0.48 +/- 0.025 in the white matter. The large increase in alpha persisted three weeks after X-irradiation. Tortuosity and non-specific uptake decreased significantly at postnatal days 2-5; at days 8-9 they were not significantly different from those of control animals, while they increased significantly at days 10-21. Less pronounced but significant changes in all three diffusion parameters were also found in areas in the ipsilateral hemisphere adjacent to directly X-irradiated cortex. Compared to the control animals [Lehmenkühler A. et al. (1993) Neuroscience 55, 339-351], a significant decrease of alpha, lambda and kappa' was found in the contralateral hemisphere 48-72 h after X-irradiation. Later, alpha values were not significantly different from those in control animals. The decrease in lambda persisted at postnatal days 4-5. A significant increase in lambda and kappa' was found at postnatal days 18-21. We conclude that X-irradiation of the brain in the early postnatal period, even when it results in only relatively light damage, still produces changes in all three diffusion parameters, particularly a large increase in extracellular space volume fraction in all cortical layers, and in the subcortical white matter. Such changes in extracellular volume fraction of the brain can contribute to impairment of signal transmission, e.g. by diluting ions and neuroactive substances released from cells, and can play an important role in functional deficits, as well as in the impairment of developmental processes. Moreover, the increase in tortuosity (inferred from the decrease in apparent diffusion coefficient) in the X-irradiated cortex, as well as in the contralateral hemisphere, suggests that, even when extracellular volume is large, the diffusion of the substances is substantially hindered.
Neuroscience 02/1996; 70(2):597-612. · 3.38 Impact Factor
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ABSTRACT: Three diffusion parameters of nervous tissue, extracellular space (ECS) volume fraction (alpha), tortuosity (gamma) and non-specific uptake (k') of tetramethylammonium (TMA+), were studied in the spinal cord of rats during experimental autoimmune encephalomyelitis (EAE). The three parameters were determined in vivo from concentration-time profiles of TMA+ using ion-selective microelectrodes. EAE was induced by injection of guinea-pig myelin basic protein (MBP), which resulted in typical morphological changes in the CNS tissue, namely inflammatory reaction, astrogliosis, blood-brain barrier (BBB) damage and paralysis. EAE was accompanied by a statistically significant increase of alpha (mean +/- S.E.M.) in the dorsal horn from 0.21 +/- 0.01 to 0.28 +/- 0.02, in the intermediate region from 0.22 +/- 0.01 to 0.33 +/- 0.02, in the ventral horn from 0.23 +/- 0.01 to 0.47 +/- 0.02 and in white matter from 0.18 +/- 0.03 to 0.30 +/- 0.03. There were significant decreases in tortuosity in the dorsal horn and in the intermediate region and decreases in non-specific uptake in the intermediate region and in the ventral horn. Although the inflammatory reaction and the astrogliosis preceded and greatly outlasted the neurological symptoms, the BBB damage had a similar time course. Moreover, there was a close correlation between the changes in extracellular space diffusion parameters and the manifestation of neurological signs. We suggest that the expansion of the extracellular space alters the diffusion properties in the spinal cord. This may affect synaptic as well as non-synaptic transmission, intercellular communication and recovery from acute EAE, and may contribute to the manifestation of neurological signs in EAE rats.
Physiological research / Academia Scientiarum Bohemoslovaca 02/1996; 45(1):11-22. · 1.55 Impact Factor
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ABSTRACT: Extracellular space (ECS) volume fraction (alpha), ECS tortuosity (lambda), and nonspecific uptake (k'), three parameters affecting the diffusion of substances in nervous tissue, were studied during ischemia and anoxia in the rat spinal cord gray matter in vivo. Progressive ischemia evoked by exsanguination, as well as anoxia evoked by respiratory or cardiac arrest, produced prominent extracellular K+ and pH changes closely related to a decrease in blood pressure and amplitude of field potentials. With use of ion-selective microelectrodes, the changes in the diffusion parameters were measured by quantitative analysis of concentration-time profiles of tetramethylammonium (TMA+) applied by iontophoresis concomitantly with ionic shifts. Under normoxic conditions (in rats with blood pressure of 80-110 mm Hg) diffusion parameters in the dorsal horn gray matter at depth 500-900 microns were as follows: alpha = 0.20 +/- 0.019, lambda = 1.62 +/- 0.12, k' = 4.6 +/- 2.5 x 10(-3) s-1 (mean +/- SD, n = 39). Extracellular K+, pH, and diffusion properties gradually changed during progressive ischemia. As the blood pressure fell to 50-60 mm Hg and field potential amplitude to 20-60%, K+ rose to 6-12 mM, pHe fell by approximately 0.05-0.1 pH unit, and volume fraction of the ECS significantly decreased, to alpha = 0.16 +/- 0.019 (n = 22). Even though the tortuosity remained virtually constant, the nonspecific uptake significantly decreased to k' = 3.4 +/- 1.8 x 10(-3) s-1. As the blood pressure fell to 20-30 mm Hg and field potential amplitude to 0-6%, K+ rose to 60-70 mM, pHe fell by approximately 0.6-0.8 pH unit, and all three diffusion parameters significantly changed. The ECS volume fraction decreased to alpha = 0.05 +/- 0.021, tortuosity increased to lambda = 2.00 +/- 0.24, and TMA+ uptake decreased to k' = 1.5 +/- 1.6 x 10(-3) s-1 (n = 12). No further increase in extracellular K+ or changes in the alpha were found during and up to 120 min after the death of the animal. However, there was a further significant increase in lambda = 2.20 +/- 0.14 and decrease in k' = 0.4 +/- 0.3 x 10(-3) s-1 (n = 24). The acid shift reached its maximum level at approximately 5-10 min after respiratory arrest and then the pHe gradually increased by approximately 0.2 unit. Full recovery to "normoxic" diffusion parameters was achieved after reinjection of the blood or after an injection of noradrenaline during severe ischemia, if this resulted in a rise in blood pressure above 80 mm Hg and a decrease in extracellular K+ below 12 mM.(ABSTRACT TRUNCATED AT 400 WORDS)
Journal of Cerebral Blood Flow & Metabolism 04/1994; 14(2):301-11. · 5.01 Impact Factor
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ABSTRACT: Extracellular space volume fraction, tortuosity and nonspecific uptake of tetramethylammonium--three diffusion parameters of brain tissue--were measured in gray matter of the somatosensory neocortex and subcortical white matter of the rat during postnatal development. The three parameters were determined from concentration-time profiles of tetramethylammonium in postnatal days 2-120 in vivo. Tetramethylammonium concentration was measured with ion-selective microelectrodes positioned 130-200 microns from an iontophoretic source. Data were correlated with cytoarchitectonic structure and average thickness of the regions in 0-90-day-old rats using rapidly frozen tissue. Extracellular space volume fraction was largest in the newborn rats and diminished with age. In two-to three-day-old animals, volume fraction (mean +/- S.E.) was 0.36 +/- 0.04 in layers III and IV, 0.38 +/- 0.02 in layer V, 0.41 +/- 0.01 in layer VI and 0.46 +/- 0.01 in white matter. The earliest decrease in volume fraction was found in layers V and VI at postnatal days 6-7 followed by a decrease in layer III and IV at postnatal days 8-9 and in white matter at postnatal days 10-11. A further dramatic reduction in volume fraction occurred in all cortical layers and especially in the white matter between postnatal days 10 and 21. There was no further decrease in volume fraction between postnatal day 21 and adults (90-120 days old). The adult volume fraction values were: layer II, 0.19 +/- 0.002; III, 0.20 +/- 0.004; IV, 0.21 +/- 0.003; V, 0.22 +/- 0.003; VI, 0.23 +/- 0.007; white matter, 0.20 +/- 0.008. Values of tortuosity ranged between 1.51 and 1.65, nonspecific cellular uptake varied from 3.3 x 10(-3)/s to 6.3 x 10(-3)/s. The variations in each parameter were not statistically significant at any age. These data represent the first characterization of diffusion parameters in a developing brain. They confirm previous histological indications of a relatively large extracellular volume fraction during early postnatal development. The constancy of the tortuosity shows that diffusion of small molecules is no more hindered in the developing brain than in the adult. The large extracellular space volume fraction of the neonatal brain could significantly dilute ions, metabolites and neuroactive substances released from cells, relative to release in adults, and may be a factor in preventing anoxia, seizure and spreading depression in young animals. The diffusion characteristics could also play an important role in the developmental process itself.
Neuroscience 08/1993; 55(2):339-51. · 3.38 Impact Factor
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ABSTRACT: Activity-related transient changes in extracellular K+ concentration ([K+]c), extracellular pH (pHc), and extracellular volume (EC volume) were studied by means of ion-selective microelectrodes in the adult rat spinal cord in vivo and in neonatal rat spinal cords isolated from pups 3-14 days of age. Repetitive electrical nerve stimulation (10-100 Hz) in adults elicited increases in [K+]c by about 2.0-3.5 mM, followed by a poststimulation K+ undershoot and triphasic alkaline-acid-alkaline changes in pHc. In 3- to 6-day-old pups, the [K+]c increased by as much as 6.5 mM at a stimulation frequency of 10 Hz, and this was accompanied by an alkaline shift. Increases in [K+]c as large as 1.3-2.5 mM accompanied by an alkaline shift were evoked by a single electrical stimulus. Stimulation in 10- to 13-day-old pups produced smaller [K+]c change and an acid shift, which was preceded by a small initial alkaline shift, as in adult rats. We conclude that glial cells buffer the activity-related [K+]c increase and alkaline pHc shifts. Mg2+ blocked the alkaline but not the acid shift. Acetazolamide had no effect on the alkaline shift but blocked the acid shift. The alkaline shift was enhanced and the acid shift blocked by Ba2+, amiloride, 4-acetamido-4'-isothiocyanotostilbene-2,2'-disulfonic acid (SITS), and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS). Activity-related acid shifts therefore have a complex mechanism, which includes Na+H+ exchange, Cl-/HCO3- exchange, or Na+/Cl-/H+/HCO3- antiport, Na(+)-HCO3- cotransport, and H+ efflux through voltage-sensitive H+ channels.(ABSTRACT TRUNCATED AT 250 WORDS)
Canadian Journal of Physiology and Pharmacology 02/1992; 70 Suppl:S301-9. · 1.95 Impact Factor
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Progress in brain research 02/1992; 94:47-56. · 3.04 Impact Factor
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Progress in brain research 02/1992; 94:109-15. · 3.04 Impact Factor
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ABSTRACT: Double-barrelled potassium and tetramethylammonium-sensitive microelectrodes were used in diffusion studies with tetramethylammonium ions, which remain essentially extracellular during the measurements. Activity-related changes in the extracellular space (ECS) volume fraction (alpha), ECS tortuosity (lambda) and the dynamics of the ECS volume changes were examined in the spinal dorsal horns of rats. The alpha and lambda in L4 and L5 segments of unstimulated rats were alpha = 0.24 +/- 0.01 (i.e. ECS occupied 24 +/- 1% of the total spinal cord volume) and lambda = 1.54 +/- 0.04 (mean +/- S.D. of mean, n = 21). The values were not significantly different throughout the dorsal horn. Repetitive electrical stimulation of peripheral nerves at 3-100 Hz increased extracellular potassium concentration [( K+]e) and ECS volume in Rexed laminae III-V by 15.8 +/- 2.7% (n = 5). After the end of stimulation, when the [K+]e decreased below the original baseline (K+ undershoot), the ECS volume decreased by 20-45%. The magnitude and duration of ECS volume decrease were positively related to the stimulation frequency and duration. The ECS volume decrease was maximal at 2-10 min after the stimulation had been discontinued, and it returned to the prestimulation values in 15-40 min. The ECS volume decreased by 20-50% after injury of the ipsilateral hind paw evoked either by subcutaneous injection of turpentine (n = 5), or by thermal injury (n = 6). The maximal changes were found in Rexed laminae III-V, 5-10 min after injection of turpentine and 10-25 min after thermal injury, and persisted for more than 120 min and 30 min, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Brain Research 10/1991; 560(1-2):216-24. · 2.73 Impact Factor
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K. T. Ng,
M. E. Gibbs,
S. F. Crowe,
G. L. Sedman,
F. Hua,
W. Zhao,
B. O'Dowd,
N. Rickard,
C. L. Gibbs,
E. Syková, J. Svoboda,
P. Jendelová
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ABSTRACT: Studies with neonate chicks, trained on a passive avoidance task, suggest that at least two shorter-term memory stages precede
long-term, protein synthesis-dependent memory consolidation. Posttetanic neuronal hyperpolarization arising from two distinct
mechanisms is postulated to underlie formation of these two early memory stages. Maintenance of the second of these stages
may involve a prolonged period of hyperpolarization brought about by phosphorylation of particular proteins. A triggering
mechanism for long-term consolidation is postulated to occur at a specific time during the second stage, and may involve reinforcement-contingent
release of neuronal noradrenaline stimulating cAMP-dependent intracellular processes. The possibility that astroglia may have
a critical role to play in these early stages of memory processing is raised.
Molecular Neurobiology 05/1991; 5(2):333-350. · 5.74 Impact Factor
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ABSTRACT: The concentration of K+ [( K+]) was measured in the cerebrospinal fluid (CSF) and in the extracellular fluid [( K+]e) in the medial forebrain of two-day-old chicks by means of K(+)-sensitive microelectrodes (K-ISM). The K-ISM potential in the CSF was compared with that in artificial CSF with 3, 4 or 6 mmol/l of [K+]. The [K+] found in CSF was 3.79 +/- 0.57 (n = 8), in the hyperstriatum accessorium (HA) 3.70 +/- 0.32 (n = 13) and in the neostriatum (N) 3.51 +/- 0.32 (n = 13; mmol/l; mean +/- SEM). Trains of local electrical stimuli (10-100 Hz, 30 sec) applied to the surface of the forebrain increased [K+]e in both HA and N by 11-13 mmol/l. Increases in [K+]e in the ectostriatum (E) of 5-6 mmol/l was found in response to electrical stimulation (30-100 Hz, 5-10 sec) of the contralateral optic nerve, and of about 2 mmol/l by applying pressure to the bulb. In chicks adapted to the dark, stimulation of the contralateral eye or both eyes with bright light flashes (1-2 Hz) or with continuous light resulted in an increase in [K+]e of 0.5-1.0 mmol/l. Smaller increases in [K+]e of 0.15-1.25 mmol/l were found in HV and N after the application of a small quantity (0.1 ml) of the chemical taste aversant methylanthranilate (MeA) or the electrical stimulation of the beak by two needle electrodes inserted into the palatum or into the tongue. After application of MeA the increase in [K+]e began 3-4 min after application and persisted for 20 min.(ABSTRACT TRUNCATED AT 250 WORDS)
Brain Research Bulletin 05/1990; 24(4):569-75. · 2.82 Impact Factor
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ABSTRACT: Regional differences in extracellular pH (pHe) were found in unstimulated rat spinal cord using double-barrel pH-sensitive microelectrodes. The pHe in the lower dorsal horn (laminae III-VII) was about 7.15, i.e. by about 0.2 pH units lower than that measured in the cerebrospinal fluid. Transient acid shifts in pHe by 0.01-0.05 pH units were found when acute nociceptive stimuli (pinch, press, heat) were applied to the hind paw. Chemical or thermal injury evoked by subcutaneous injection of turpentine or by application of 1-3 ml of hot oil onto the hindpaw produced a long-term decrease in pHe base line in the lower dorsal horn by about 0.05-0.1 pH units. The decrease in pHe began 2-10 min after injury and persisted for more than 2 h. Electrical nerve stimulation (10-100 Hz, 20-60 s) elicited biphasic (acid-alkaline) or triphasic (alkaline-acid-alkaline) changes in pHe which have a similar depth profile as the concomitantly recorded increase in [K+]e. An initial alkaline shift by about 0.005 pH units was found to be significantly decreased by La3+, an H+ channel blocker. The dominating acid shift by about 0.1-0.2 pH units was accelerated and increased by acetazolamide (carbonic anhydrase inhibitor) showing that the high buffering capacity of the extracellular fluid may hamper the resolution of acid perturbations. Stimulation-evoked acid shifts were blocked by amiloride, SITS, DIDS and La3+ and therefore have a complex mechanism which includes Na+/H+ exchange, Cl-/HCO3- cotransport and/or Na+/Cl-/H+/HCO3- antiport and H+ efflux through voltage-sensitive H+ channels. The poststimulation alkaline shift (alkaline undershoot) was blocked by ouabain and reflects coupled clearance of K+ and H+ by active transport processes.
Brain Research 05/1990; 512(2):181-9. · 2.73 Impact Factor
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ABSTRACT: Changes in extracellular K+ concentration ([K+]e) in dorsal horn were studied by means of double-barrel K+-sensitive microelectrodes in rats anesthetized with Nembutal. Acute nociceptive stimuli (pinch, press, heat) applied to the hind paw induced a transient increase in [K+]e of about 0.1-0.5 mM which persisted for 5-30 s. Regional variations in [K+]e were found in unstimulated rat spinal cords. The K+ level in the lower dorsal horn (laminae III-V) was by about 0.4 +/- 0.06 mM higher than that in more superficial laminae and in the ventral horn. Chemical or thermal injury was evoked by: s.c. injection of 0.1-0.5 ml formalin or turpentine into the hind paw, by application of mustard oil onto the skin, or by thermal injury of the hind paw. These produced a long-term increase in [K+]e in the lower dorsal horn by 0.3-3.0 mM in 75% of animals (n = 27). The increase in [K+]e began 5-15 min after injury and persisted for more than 2 h. In the rest of the animals, occasional elevation in [K+]e of 0.1-0.3 mM were observed. The K+ increases evoked by acute nociceptive stimuli as well as by injury were blocked by preinjecting the hind paw with 1% procaine. However, when procaine was applied 20 min or later after injury, the evoked long-term rise in [K+]e was not affected. This shows that the long-term K+ accumulation results from self-sustained abnormal neuronal firing induced in the dorsal horn by injury.(ABSTRACT TRUNCATED AT 250 WORDS)
Brain Research 09/1988; 458(1):97-105. · 2.73 Impact Factor
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ABSTRACT: The use of ion-sensitive microelectrodes enabled us to follow the dynamic changes in extracellular pH (pHe) together with those in the extracellular concentration of some biologically important ions, particularly K+ and Ca2+. Activity-related changes in pHe were studied in isolated spinal cords of frogs and in spinal cords of rats in vivo. Repetitive electrical stimulation of an afferent input led either to triphasic alkaline-acid-acid changes (90% of frogs) or to triphasic alkaline-acid-alkaline changes (10% of frogs and rats) with the greatest changes in the lower dorsal horns. The transient acid shift by as much as 0.15-0.25 pH units is dominant and builds up during the stimulation. The changes in pHe were also found in response to various adequate stimuli applied to the skin on the hind limb. Using specific inhibitors of Na+/H+ exchange, K+-Cl- co-transport, Cl-/HCO3- exchange, the Na+/K+ pump and carbonic anhydrase, we found pHe homeostasis to be impaired and stimulation-induced changes in pHe decreased. We conclude that the pHe changes evoked by electrical or adequate stimulation of an afferent input are not determined by changes in extracellular strong ion concentration differences due to accumulation of lactate, since we found no effect of NaF, a metabolic blocker of lactate production. However, lactate accumulation has been demonstrated during seizures, spreading depression and anoxia. Recently, it has been recognized that the observed pHe changes can affect permeability of membrane ionic channels, neuronal excitability and glial cell function.
Ciba Foundation symposium 02/1988; 139:220-35.
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ABSTRACT: Changes in extracellular K+ concentration ([K+]e) in dorsal horn were studied by means of double-barrel K+-sensitive microelectro in rats anesthetized with Nembutal. Acute nociceptive stimuli (pinch, press, heat) applied to the hind paw induced a transient increase in [K+]e of about 0.1–0.5 mM which persisted for 5–30 s. Regional variations in [K+]e were found in unstimulated rat spinal cords. The K+ level in the lower dorsal horn (laminae III–V) was by about0.4 ± 0.06mM higher than that in more superfical laminae and in the ventral horn. Chemical or thermal injury was evoked by: s.c. injection of 0.1–0.5 ml formalin or turpentine into the hind paw, by application of mustard oil onto the skin, or by thermal injury of the hind paw. These produced a long-term increase in [K+]e in the lower dorsal horn by 0.3–3.0 mM in 75% of animals (n = 27). The increase in [K+]e began 5–15 min after injury and persisted for more than 2 h. In the rest of the animals, occasional elevations in [K+]e of 0.1–0.3 mM were observed. The K+ increases evoked by acute nociceptive stimuli as well as by injury were blocked by preijecting the hind paw with 1% procaine. However, when procaine was applied 20 min or later after injury, the evoked long-term rise in [K+]e was not affected. This shows that the long-term K+ accumulation results from self-sustained abnormal neuronal firing induced in the dorsal horn by injury. It is suggested that the increase in [K+]e in dorsal horn following peripheral injury can modify spinal cord transmission and possibly contribute to post-injury sensory disorders
Brain Research.
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ABSTRACT: Three diffusion parameters of brain tissue, extracellular space volume fraction (α), tortuosity (λ) and non-specific uptake (κ′) of tetramethylammonium were studied in the somatosensory neocortex and subcortical white matter of the rat during postnatal development (postnatal days 2–21) after X-irradiation at postnatal days 0–1. The diffusion parameters were determined from extracellular concentration-time profiles of tetramethylammonium. The tetramethylammonium concentration was measuredin vivo with ion-selective microelectrodes positioned 130–200 μm from an iontophoretic source. X-irradiation with a single dose of 40 Gy resulted in typical early morphological changes in the tissue, namely cell death, DNA fragmentation, extensive neuronal loss, blood-brain barrier damage, activated macrophages, astrogliosis, increase in extracellular fibronectin and concomitant changes in all three diffusion parameters. The changes were observed as early as 48 h post-irradiation (at postnatal days 2–3) and still persisted at postnatal day 21. On the other hand, X-irradiation with a single dose of 20 Gy resulted in relatively light neuronal damage and loss, while blood-brain barrier damage, astrogliosis and changes in diffusion parameters were not significantly different from those found with 40 Gy.It is known that the volume fraction of the extracellular space in the non-irradiated cortex is large in newborn rats and diminishes with age [Lehmenkühler A.et al. (1993)Neuroscience55, 339–351]. X-irradiation with a single dose of 40 or 20 Gy blocked the normal pattern of volume fraction decrease during postnatal development, and in fact brought about a significant increase. At postnatal days 4–5, α increased to 0.49 ± 0.036 in layer III, 0.51 ± 0.042 in layer IV, 0.48 ± 0.02 in layer V, 0.48 ± 0.028 in layer VI and 0.48 ± 0.025 in the white matter. The large increase in α persisted three weeks after X-irradiation. Tortuosity and non-specific uptake decreased significantly at postnatal days 2–5; at days 8–9 they were not significantly different from those of control animals, while they increased significantly at days 10–21. Less pronounced but significant changes in all three diffusion parameters were also found in areas in the ipsilateral hemisphere adjacent to directly X-irradiated cortex. Compared to the control animals [Lehmenkühler A.et al. (1993)Neuroscience55, 339–351], a significant decrease of α, λ and κ′ was found in the contralateral hemisphere 48–72 h after X-irradiation. Later, α values were not significantly different from those in control animals. The decrease in λ persisted at postnatal days 4–5. A significant increase in λ and κ′ was found at postnatal days 18–21.We conclude that X-irradiation of the brain in the early postnatal period, even when it results in only relatively light damage, still produces changes in all three diffusion parameters, particularly a large increase in extracellular space volume fraction in all cortical layers, and in the subcortical white matter. Such changes in extracellular volume fraction of the brain can contribute to impairment of signal transmission, e.g. by diluting ions and neuroactive substances released from cells, and can play an important role in functional deficits, as well as in the impairment of developmental processes. Moreover, the increase in tortuosity (inferred from the decrease in apparent diffusion coefficient) in the X-irradiated cortex, as well as in the contralateral hemisphere, suggests that, even when extracellular volume is large, the diffusion of the substances is substantially hindered.
Neuroscience.
