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Biomedical subjects

R Raghupathi

Publications and source records attributed to R Raghupathi.

At least 55 records · Page 3Linked to original sources
PubMed1999

Increased vulnerability of NFH-LacZ transgenic mouse to traumatic brain injury-induced behavioral deficits and cortical damage.

The authors evaluated the neurobehavioral and neuropathologic sequelae after traumatic brain injury (TBI) in transgenic (TG) mice expressing truncated high molecular weight neurofilament (NF) protein fused to beta-galactosidase (NFH-LacZ), which develop Lewy body-like NF-rich inclusions throughout the CNS. TG mice and their wild-type (WT) littermates were subjected to controlled cortical impact brain injury (TG, n = 19; WT, n = 17) or served as uninjured controls (TG, n = 11; WT, n = 11). During a 3-week period, mice were evaluated with an array of neuromotor function tests including neuroscore, beam balance, and both fast and slow acceleration rotarod. Brain-injured WT and TG mice showed significant motor dysfunction until 15 days and 21 days post-injury, respectively (P<.025). Compared with brain-injured WT mice, brain-injured TG mice had significantly greater motor dysfunction as assessed by neuroscore (P<.01) up to and including 15 days post-injury. Similarly, brain-injured TG mice performed significantly worse than brain-injured WT mice on slow acceleration rotarod at 2, 8, and 15 days post-injury (P<.05), and beam balance over 2 weeks post-injury (P<.01). Histopathologic analysis showed significantly greater tissue loss in the injured hemisphere in TG mice at 4 weeks post-injury (P<.01). Together these data show that NFH-LacZ TG mice are more behaviorally and histologically vulnerable to TBI than WT mice, suggesting that the presence of NF-rich inclusions may exacerbate neuromotor dysfunction and cell death after TBI.

Animals↗
PubMed1999

Interleukin-1 receptor antagonist attenuates regional neuronal cell death and cognitive dysfunction after experimental brain injury.

The effect of systemic administration of human recombinant interleukin-1 receptor antagonist (rhIL-1ra) on behavioral outcome and histopathologic damage after lateral fluid-percussion brain injury of moderate severity was evaluated. In study 1, brain-injured Sprague Dawley rats received timed subcutaneous injections beginning 15 minutes after injury of either 100 mg/kg rhIL-1ra (high dose, total dose = 1900 mg/kg), 10 mg/kg rhIL-1ra (low dose, total dose = 190 mg/kg), or vehicle over 7 days. No effect of low-dose rhIL-1ra was observed in study 1. High-dose rhIL-1ra significantly attenuated posttraumatic neuronal loss in the injured hippocampal CA3 region (P < 0.05), dentate hilus (P < 0.05), and cortex (P < 0.05) but impaired recovery of motor function at 7 days after trauma (P < 0.05). In study 2, rats were pretrained to learn a visuospatial task in a Morris water maze, subjected to fluid-percussion brain injury or sham treatment, and randomly assigned to receive multiple subcutaneous injections at timed intervals of 100 mg/kg rhIL-1ra (total dose = 900 mg/kg) or vehicle over 42 hours, followed by continuous infusion of a lower concentration of rhIL-1ra (20 mg/kg/day, total dose = 100 mg/kg), or vehicle for 5 days using subcutaneously implanted osmotic minipumps. Postinjury administration of rhIL-1ra significantly attenuated cognitive deficits compared with vehicle-treated animals at 42 hours (P < 0.05) but did not affect motor function at 48 hours, 1 week, and 2 weeks. These results suggest that inhibitors of cytokine pathways may be therapeutically useful for the treatment of brain trauma.

Animals↗
PubMed1999

Survival and integration of transplanted postmitotic human neurons following experimental brain injury in immunocompetent rats.

OBJECT: Limitations regarding cell homogeneity and survivability do not affect neuronlike hNT cells, which are derived from a human teratocarcinoma cell line (Ntera2) that differentiates into postmitotic neurons with exposure to retinoic acid. Because NT2N neurons survive longer than 1 year after transplantation into nude mice brains, the authors grafted these cells into the brains of immunocompetent rats following lateral fluid-percussion brain injury to determine the long-term survivability of NT2N cell grafts in cortices damaged by traumatic brain injury (TBI) and the therapeutic effect of NT2N neurons on cognitive and motor deficits. METHODS: Seventy-two adult male Sprague-Dawley rats, each weighing between 340 and 370 g, were given an anesthetic agent and subjected to lateral fluid percussion brain injury of moderate severity (2.2-2.5 atm in 46 rats) or to surgery without TBI (shamoperation, 26 rats). Twenty-four hours postinjury, 10(5) NT2N cells (24 injured animals) or 3 microl of vehicle (22 injured and 14 control animals) was stereotactically implanted into the periinjured or control cerebral cortex. Motor function was assessed at weekly intervals and all animals were killed at 2 or 4 weeks after their posttraumatic learning ability was assessed using a Morris water maze paradigm. Viable NT2N grafts were routinely observed to extend human neural cell adhesion molecule-(MOC-1)immunoreactive processes into the periinjured cortex at 2 and 4 weeks posttransplantation, although no significant improvement in motor or cognitive function was noted. Inflammation identified around the transplant at both time points was assessed by immunohistochemical identification of macrophages (ED-1) and microglia (isolectin B4). CONCLUSIONS: Long-term survival and integration of NT2N cells in the periinjured cortex of immunocompetent rats provides the researcher with an important cellular system that can be used to study maturation, regulation, and neurite outgrowth of transplanted neurons following TBI.

Animals↗
PubMed1998

Experimental brain injury induces regionally distinct apoptosis during the acute and delayed post-traumatic period.

The temporal pattern of apoptosis in the adult rat brain after lateral fluid-percussion (FP) brain injury was characterized using terminal deoxynucleotidyl-transferase-mediated biotin-dUTP nick end labeling (TUNEL) histochemistry and agarose gel electrophoresis. Male Sprague Dawley rats were subjected to brain injury and killed for histological analysis at intervals from 12 hr to 2 months after injury (n = 3/time point). Sham (uninjured) controls were subjected to anesthesia with (n = 3) or without (n = 3) surgery. Apoptotic TUNEL-positive cells were defined using stringent morphological criteria including nuclear shrinkage and fragmentation and condensation of chromatin and cytoplasm. Double-labeled immunocytochemistry was performed to identify TUNEL-positive neurons (anti-neurofilament monoclonal antibody RM044), astrocytes (anti-glial fibrillary acidic protein polyclonal antibody), and oligodendrocytes (anti-cyclic nucleotide phosphohydrolase polyclonal antibody). Compared with that seen with sham controls, in the injured cortex, significant apoptosis occurred at 24 hr (65 +/- 19 cells; p < 0.05) with a second, more pronounced response at 1 week after injury (91 +/- 24 cells; p < 0.05). The number of apoptotic cells in the white matter was increased as early as 12 hr after injury and peaked by 1 week (33 +/- 6 cells; p < 0.05). An increase in apoptotic cells was observed in the hippocampus at 48 hr (13 +/- 8), whereas in the thalamus, the apoptotic response was delayed, peaking at 2 weeks after injury (151 +/- 71 cells; p < 0.05). By 2 months, the number of apoptotic cells in most regions had returned to uninjured levels. At 24 hr after injury, TUNEL-labeled neurons and oligodendrocytes were localized primarily to injured cortex. By 1 week after injury, populations of TUNEL-labeled astrocytes and oligodendrocytes were present in the injured cortex, while double-labeled neurons were present predominantly in injured cortex and thalamus, with a few scattered in the hippocampus. DNA agarose gels confirmed morphological identification of apoptosis. These data suggest that the apoptotic response to trauma is regionally distinct and may be involved in both acute and delayed patterns of cell death.

Analysis of Variance↗
PubMed1998

Riluzole attenuates cortical lesion size, but not hippocampal neuronal loss, following traumatic brain injury in the rat.

The neuroprotective effects of Riluzole, a compound with several mechanisms of action including the inhibition of sodium channel activity and glutamate release, were evaluated in a rat model of parasagittal fluid-percussion (FP) brain injury. Male Sprague-Dawley rats (350-400 g, n = 17) were anesthetized with sodium pentobarbital (60 mg/kg i.p.) and subjected to parasagittal FP brain injury of moderate severity (2.3-2.5 atm). Fifteen min following injury, animals randomly received an i.v. bolus of either Riluzole (8 mg/kg, n = 8) or vehicle (n = 9), followed by subcutaneous injections (identical dose) at 6 hr and 24 hr. Two weeks after injury and drug treatment, animals were sacrificed and a series of brain sections, stained with Hematoxylin and Eosin (H&E) or cresyl violet, were evaluated for quantitative cortical lesion volume and cell counts of hippocampal CA3 neurons, respectively, using a computerized image analysis system. Administration of Riluzole significantly reduced FP-induced tissue loss in the temporal/occipital cortices ipsilateral to the site of impact by 46%, compared to vehicle-treated, brain-injured animals (P = 0.01). In contrast, the selective neuronal loss observed in the CA3 region of the ipsilateral hippocampus was unaffected by Riluzole treatment. The present study demonstrates that Riluzole can attenuate cortical lesion size following brain trauma. These neuroprotective effects may be related to the synergy of the different mechanisms of action of Riluzole.

Animals↗
PubMed1998

Twofold overexpression of human beta-amyloid precursor proteins in transgenic mice does not affect the neuromotor, cognitive, or neurodegenerative sequelae following experimental brain injury.

By using transgenic mice that overexpress human beta-amyloid precursor proteins (APPs) at levels twofold higher than endogenous APPs, following introduction of the human APP gene in a yeast artificial chromosome (YAC), we examined the effects of controlled cortical impact (CCI) brain injury on neuromotor/cognitive dysfunction and the development of Alzheimer's disease (AD)-like neuropathology. Neuropathological analyses included Nissl-staining and immunohistochemistry to detect APPs, beta-amyloid (Abeta), neurofilament proteins, and glial fibrillary acidic protein, whereas Abeta levels were measured in brain homogenates from mice subjected to CCI and control mice by using a sensitive sandwich enzyme-linked immunosorbent assay. Twenty APP-YAC transgenic mice and 17 wild type (WT) littermate controls were anesthetized and subjected to CCI (velocity, 5 m/second; deformation depth, 1 mm). Sham (anesthetized but uninjured) controls (n = 10 APP-YAC; n = 8 WT) also were studied. Motor function was evaluated by using rotarod, inclined-plane, and forelimb/hindlimb flexion tests. The Morris water maze was used to assess memory. Although CCI induced significant motor dysfunction and cognitive deficits, no differences were observed between brain-injured APP-YAC mice and WT mice at 24 hours and 1 week postinjury. By 1 week postinjury, both cortical and hippocampal CA3 neuron loss as well as extensive astrogliosis were observed in all injured animals, suggesting that overexpression of human APPs exhibited no neuroprotective effects. Although AD-like pathology (including amyloid plaques) was not observed in either sham or brain-inj ured animals, a significant decrease in brain concentrations of only Abeta terminating at amino acid 40 (Abeta x-40) was observed following brain injury in APP-YAC mice (P < 0.05 compared with sham control levels). Our data show that the APP-YAC mice do not develop AD-like neuropathology following traumatic brain injury. This may be because this injury does not induce elevated levels of the more amyloidogenic forms of human Abeta (i.e., Abeta x-42/43) in these mice.

Amyloid beta-Peptides↗
PubMed1998

Brain trauma induces massive hippocampal neuron death linked to a surge in beta-amyloid levels in mice overexpressing mutant amyloid precursor protein.

Although brain trauma is a risk factor for Alzheimer's disease, no experimental model has been generated to explore this relationship. We developed a model of brain trauma in transgenic mice that overexpress mutant human amyloid precursor protein (PDAPP) leading to the appearance of Alzheimer's disease-like beta-amyloid (Abeta) plaques beginning at 6 months of age. We induced cortical impact brain injury in the PDAPP animals and their wild-type littermates at 4 months of age, ie, before Abeta plaque formation, and evaluated changes in posttraumatic memory function, histopathology, and regional tissue levels of the Abeta peptides Abeta1-40 and Abeta1-42. We found that noninjured PDAPP mice had impaired memory function compared to noninjured wild-type littermates (P < 0.01) and that brain-injured PDAPP mice had more profound memory dysfunction than brain-injured wild-type littermates (P < 0.001). Although no augmentation of Abeta plaque formation was observed in brain-injured PDAPP mice, a substantial exacerbation of neuron death was found in the hippocampus (P < 0.001) in association with an acute threefold increase in Abeta1-40 and sevenfold increase in Abeta1-42 levels selectively in the hippocampus (P < 0.01). These data suggest a mechanistic link between brain trauma and Abeta levels and the death of neurons.

Amyloid beta-Peptides↗
PubMed1998

The Dorothy Russell Memorial Lecture. The molecular and cellular sequelae of experimental traumatic brain injury: pathogenetic mechanisms.

The mechanisms underlying secondary or delayed cell death following traumatic brain injury (TBI) are poorly understood. Recent evidence from experimental models of TBI suggest that diffuse and widespread neuronal damage and loss is progressive and prolonged for months to years after the initial insult in selectively vulnerable regions of the cortex, hippocampus, thalamus, striatum, and subcortical nuclei. The development of new neuropathological and molecular techniques has generated new insights into the cellular and molecular sequelae of brain trauma. This paper will review the literature suggesting that alterations in intracellular calcium with resulting changes in gene expression, activation of reactive oxygen species (ROS), activation of intracellular proteases (calpains), expression of neurotrophic factors, and activation of cell death genes (apoptosis) may play a role in mediating delayed cell death after trauma. Recent data suggesting that TBI should be considered as both an inflammatory and/or a neurodegenerative disease is also presented. Further research concerning the complex molecular and neuropathological cascades following brain trauma should be conducted, as novel therapeutic strategies continue to be developed.

Animals↗
PubMed1998

Increased jun immunoreactivity in an in vitro model of mammalian spinal neuron physical injury.

Dendrites were transected from murine spinal neurons. Unlesioned neurons showed dark nucleolar and patchy cytoplasmic jun immunostaining. By 0.5 and 2 h, most lesioned neurons stained intensely throughout the soma. However, at 24 h only dead neurons displayed intense somal staining, and 100% of the surviving cells stained like unlesioned controls. Correlation of immunostaining patterns with viability, injury, and death suggests jun gene expression may influence the survival of neurons after physical injury.

Animals↗
PubMed1998

BCL-2 overexpression attenuates cortical cell loss after traumatic brain injury in transgenic mice.

The proto-oncogene, BCL-2, has been suggested to participate in cell survival during development of, and after injury to, the CNS. Transgenic (TG) mice overexpressing human Bcl-2 (n = 21) and their wild-type (WT) littermates (n = 18) were subjected to lateral controlled cortical impact brain injury. Lateral controlled cortical impact brain injury resulted in the formation of a contusion in the injured cortex at 2 days, which developed into a well-defined cavity by 7 days in both WT and TG mice. At 7 days after injury, brain-injured TG mice had a significantly reduced cortical lesion (volume = 1.99 mm3) compared with that of the injured WT mice (volume = 5.1 mm3, P < 0.01). In contrast, overexpression of BCL-2 did not affect the extent of hippocampal cell death after lateral controlled cortical impact brain injury. Analysis of motor function revealed that both brain-injured WT and TG mice exhibited significant right-sided deficits at 2 and 7 days after injury (P < 0.05 compared with the uninjured controls). Although composite neuroscores (sum of scores from forelimb and hind limb flexion, lateral pulsion, and inclined plane tests) were not different between WT and TG brain-injured mice, TG mice had a slightly but significantly reduced deficit in the inclined plane test (P < 0.05 compared to the WT mice). These data suggest that the cell death regulatory gene, BCL-2, may play a protective role in the pathophysiology of traumatic brain injury.

Animals↗
PubMed1998

Pharmacotherapy for traumatic brain injury: a review.

Traumatic brain injury in the United States is a serious health problem: it is a significant factor in approximately half of all trauma-related deaths, and, leads to persistent, long-term neurologic dysfunction in survivors. Physiological changes that accompany brain trauma such as cardiovascular alterations, hypercapnia, hypoxiaischemia, metabolic dysfunction, and alterations in the endogenous neurochemical systems are associated with poor clinical outcome. Using a variety of animal models, experimental studies have begun to elucidate these neurochemical disturbances that underlie the behavioral deficits and the pathologic outcome. Modification of the post-traumatic neurochemical milieu can promote functional recovery. While a number of currently available pharmaceutical compounds have been reported to be effective in various animal models of TBI, their utility in the clinical setting has been disappointing [119]. New hope has arisen for the treatment of TBI, based upon new research findings regarding the development of novel pharmacological therapies for brain trauma. Reduction of brain temperature can maintain relative tissue homeostasis by lowering metabolic activity. Hypothermia has been attempted in patients over the past 50 years and recent experimental evidence suggests that posttraumatic hypothermia can attenuate EAA release and free-radical production [120]. In animal models, hypothermic treatment has attenuated post-traumatic neurologic motor dysfunction [121,122], improved histopathologic damage [123,124], and reduced the extent of cytoskeletal damage [120]. In addition, the armamentarium of potentially neuroprotective compounds, which has increased rapidly in the recent years, provides promising pharmacological therapies for the treatment of TBI.

Animals↗
PubMed1997

Remacemide hydrochloride reduces cortical lesion volume following brain trauma in the rat.

We evaluated the therapeutic effects of remacemide hydrochloride, an N-methyl-D-aspartate (NMDA) receptor-associated ionophore blocker with sodium channel blocking activity, on cortical lesion volume and memory dysfunction following parasagittal fluid-percussion brain injury in the anesthetized rat. We found that intravenous (i.v.) administration 15 min following injury of remacemide hydrochloride at both 25 and 10 mg/kg significantly reduced posttraumatic cortical lesion volume (P < 0.05), measured at 48 h postinjury using a tetrazolium salt tissue staining technique. However, neither of these doses nor the dosing regimen of 25 mg/kg i.v. 15 min postinjury plus a subcutaneous infusion over 24 h of 20 mg/kg remacemide hydrochloride improved posttraumatic memory function determined by a Morris water maze paradigm.

Acetamides↗
PubMed1997

Insulin-like growth factor-1 (IGF-1) improves both neurological motor and cognitive outcome following experimental brain injury.

We evaluated the efficacy of insulin-like growth factor-1 (IGF-1) in attenuating neurobehavioral deficits following lateral fluid percussion (FP) brain injury. Male Sprague-Dawley rats (345-425 g, n = 88) were anesthetized and subjected to FP brain injury of moderate severity (2.4-2.9 atm). In Study 1, IGF-1 (1.0 mg/kg, n = 9) or vehicle (n = 14) was administered by subcutaneous injection at 15 min postinjury and similarly at 12-h intervals for 14 days. In animals evaluated daily for 14 days, IGF-1 treatment attenuated motor dysfunction over the 2-week period (P < 0.02). In Study 2, IGF-1 (4 mg/kg/day, n = 8 uninjured, n = 13 injured) or vehicle (n = 8 uninjured, n = 13 injured) was administered for 2 weeks via a subcutaneous pump implanted 15 min postinjury. IGF-1 administration was associated with increased body weight and mild, transient hypoglycemia which was more pronounced in brain-injured animals. At 2 weeks postinjury (P < 0.05), but not at 48 h or 1 week, brain-injured animals receiving IGF-1 showed improved neuromotor function compared with those receiving vehicle. IGF-1 administration also enhanced learning ability (P < 0.03) and memory retention (P < 0.01) in brain-injured animals at 2 weeks postinjury. Taken together, these data suggest that chronic, posttraumatic administration of the trophic factor IGF-1 may be efficacious in ameliorating neurobehavioral dysfunction associated with traumatic brain injury.

Animals↗
PubMed1997

Metabolic quantification of lesion volume following experimental traumatic brain injury in the rat.

A reliable and rapid method for quantifying lesion volume following traumatic brain injury (TBI) has vast potential in brain injury research. Staining with 2, 3, 5-triphenyltetrazolium chloride (TTC) provides for demarcation of damaged or infarcted tissue from normal, viable cerebral tissue, in which a red formazan product is formed by reduction during cellular respiration of mitochondrial dehydrogenase enzymes. The present study evaluated the use of TTC staining to quantify the cortical lesion volume in rats undergoing fluid-percussion (FP) brain injury. Male Sprague-Dawley rats (350-450 g, n = 27) were anesthetized (sodium pentobarbital, 60 mg/kg, ip) and subjected to lateral FP brain injury of mild (1.1-1.3 atm, n = 5), moderate (2.0-2.3 atm, n = 9), or high (2.4-2.6 atm, n = 8) severity, while sham (noninjured) animals (n = 5) were anesthetized and surgically prepared without injury. Forty-eight hours after injury animals were sacrificed, brains were stained with TTC, and lesion volumes were calculated. A highly significant correlation was found between cerebral cortical lesion volume (mm3) and severity of brain injury (r = 0.85; p < 0.0001). The mean (+/-SD) lesion volumes were 12.1 (+/-4.5) mm3 following mild injury, 33.8 (+/-8.6) mm3 following moderate injury, and 45.1 (+/-14.0) mm3 following severe injury. A significant difference was observed between all injury groups using a t test with Bonferroni correction (p < 0.05). These results suggest that the TTC staining technique is a useful, rapid, and reproducible method for quantification of lesion volume following lateral FP brain injury.

Animals↗
PubMed1997

Delayed administration of basic fibroblast growth factor (bFGF) attenuates cognitive dysfunction following parasagittal fluid percussion brain injury in the rat.

The present study evaluates the therapeutic effects of delayed administration of bFGF on cognitive dysfunction and histopathological damage following lateral fluid-percussion (FP) brain injury. Male Sprague-Dawley rats were trained to learn a visuospatial task in a Morris Water Maze (MWM) paradigm and then were anesthetized and subjected to either FP brain injury of moderate severity (2.5-2.8 atm, n = 32) or surgery without brain injury (n = 10). Twenty-four hours postinjury, an infusion cannula connected to a mini-osmotic pump was implanted into the area of maximal cortical injury to continuously infuse either bFGF (2.0 g) or vehicle for 7 days. Treatment with bFGF significantly attenuated posttraumatic memory dysfunction in the MWM at 8 days postinjury when compared to vehicle treatment (p < 0.05). The cortical lesion and significant cell loss in the ipsilateral CA3 region of the hippocampus, produced by FP injury, was not affected by bFGF treatment. However, immunohistochemical evaluation of glial fibrillary acidic protein revealed a trend toward increased astrocytosis in the injured cortex of bFGF-treated animals compared to vehicle-treated animals (p < 0.1). These results indicate that bFGF may be efficacious in attenuating cognitive dysfunction associated with traumatic brain injury.

Analysis of Variance↗
PubMed1996

Regionally and temporally distinct patterns of induction of c-fos, c-jun and junB mRNAs following experimental brain injury in the rat.

Lateral (parasagittal) fluid-percussion brain injury of mild (1.0-1.5 atm) and moderate (2.1-2.4 atm) severity induced expression of mRNAs for the immediate early genes (IEGs) c-fos, c-jun and junB. At 5 min following mild brain injury, c-fos and junB mRNA were co-induced in the cortex ipsilateral to the impact site. Expression remained elevated up to 2 h after injury and returned to control levels by 6 h. Levels of c-fos mRNA increased in the cells of the hippocampal dentate gyrus as early as 5 min after mild brain injury and additionally in the areas CA1-3 by 30 min. By 2 h, no hippocampal c-fos mRNA was detectable. Induction of junB mRNA in the hippocampus was delayed, occurring at 30 min after injury, and remained elevated up to 2 h post injury. Increased levels of junB mRNA were also observed in the striatum ipsilateral to the injury. Increased expression of c-jun mRNA was restricted to the ipsilateral dentate gyrus and was observed at 5 min after injury and remained elevated up to 6 h. Although the temporal pattern of induction of individual IEGs after brain injury of moderate severity was similar to that observed after mild severity, moderate injury induced IEG mRNA in both injured and contralateral hemispheres. These data suggest that traumatic brain injury invokes a complex acute regional and cellular response which may involve the activation of multiple signal transduction pathways.

Animals↗
PubMed1995

Regional induction of c-fos and heat shock protein-72 mRNA following fluid-percussion brain injury in the rat.

To evaluate the cellular response to traumatic brain injury, the expression of mRNA for c-fos and the 72-kDa heat shock protein (hsp72) was determined using in situ hybridization following lateral fluid-percussion injury (2.2-2.4 atm) in rat brain. At 2 h after injury, induction of c-fos mRNA was observed throughout the cortex ipsilateral to the site of injury, while increased expression of hsp72 mRNA was restricted to regions of the cortex surrounding the contusion area. An increase in c-fos mRNA, but not hsp72 mRNA, was observed bilaterally in the CA3 subfield of the hippocampus and the granule cells of the dentate gyrus and in the thalamus ipsilateral to the impact site. By 6 h, increased expression of c-fos mRNA was observed only in the corpus callosum on the impact side; hsp72 mRNA persisted in the deep cortical layers and upper layers of the subcortical white matter below the site of maximal injury. By 24 h, both c-fos and hsp72 mRNA had returned to control levels in all regions of the brain. These results demonstrate that lateral fluid-percussion brain injury triggers regionally and temporally specific expression of c-fos and hsp72 mRNA, which may be suggestive of differential neurochemical alterations in neurons and glia following experimental brain injury.

Animals↗