ABSTRACT
Background Acute pancreatitis has local and systemic manifestations, so it's important to assess the severity by various scoring system. Among them bed side index for severity of acute pancreatitis and pancreatitis three score have been considered to be more predictive and easier. Objective To determine the comparative prognostic value of bed side index for severity of acute pancreatitis and pancreatitis 3 score and its correlation with the outcome. Method A prospective observational study was conducted on 50 cases of acute pancreatitis. The patients were assessed clinically, radiologically and biochemically and were categorised into mild, moderate and severe category as per Atlanta Classification. Bed side index for severity of acute pancreatitis and pancreatitis 3 score was calculated at the time of admission and followed till the time of discharge or they had mortality. Result Receiver operating characteristic curve, showed bed side Index for severity of acute pancreatitis score had sensitivity (66.67%), specificity (84.09%), diagnostic accuracy (84%) while pancreatitis 3 score had sensitivity (50%), specificity (81.82%), diagnostic accuracy (80%) for the severity of acute pancreatitis. Bed side index for severity of acute pancreatitis had sensitivity (100%), specificity (66.67%) and Pancreatitis 3 score had sensitivity (66.67%), specificity (80.85%) for predicting the mortality in acute pancreatitis. Conclusion Bed side index for severity of acute pancreatitis and pancreatitis 3 score are both simple, bedside tool for assessing the severity and mortality but bed side index for severity of acute pancreatitis score had better sensitivity, specificity for assessing the severity and mortality as compared to pancreatitis three score.
Subject(s)
Pancreatitis , Humans , Acute Disease , India , Pancreatitis/diagnosis , Patient Acuity , Predictive Value of Tests , Prognosis , Severity of Illness Index , Tertiary Care Centers , Prospective StudiesABSTRACT
Medical teaching is about giving a student a collaborative experience of the art and skill of the practice of medicine. This is acquired through authentic patient experiences. A clinical teacher uses clinical lectures, simulations, lab sessions, small group interactions, cadaver dissection and technical classes (eg: ultrasound) to create a complete clinical immersion experience. For this we use both the in-patient and out-patient facilities.
Subject(s)
COVID-19 , Education, Medical, Undergraduate , Students, Medical , Cadaver , Curriculum , Dissection , Humans , SARS-CoV-2ABSTRACT
Regional levels of prostate apoptosis response-4 (Par-4) protein and mRNA were measured after lateral fluid percussion (FP) brain injury in rats. Immunochemical studies indicated that Par-4 immunoreactivity (ir) is present in cortical neurons and hippocampal CA1-CA3 pyramidal neurons in uninjured rats. Increases of Par-4-ir were observed in the CA3 neurons of the ipsilateral hippocampus (IH), but not in injured left cortex (IC) at 48 h after FP brain injury. Levels of the Par-4 mRNA measured by RT-PCR assay and protein measured by Western blot procedure were significantly increased in the injured IC and IH, but not in the contralateral right cortex and hippocampus after brain injury. Levels of both Par-4 protein and mRNA were significantly increased in the IC and IH as early as 2 h and stayed elevated at 24 and 48 h after injury. These data show that the induction of proapoptotic Par-4 mRNA and protein occurs only in the IC and IH that have been observed to undergo apoptosis and neuronal cell loss after lateral FP brain injury. Because increased expression of Par-4 has been observed to contribute to apoptosis and cell death in cultured neurons, the present temporal pattern of Par-4 expression is consistent with a role for Par-4 in apoptosis and neuronal cell death after traumatic brain injury.
Subject(s)
Brain Injuries/metabolism , Carrier Proteins/metabolism , Intracellular Signaling Peptides and Proteins , RNA, Messenger/biosynthesis , Animals , Apoptosis , Apoptosis Regulatory Proteins , Blotting, Western , Carrier Proteins/genetics , Cerebral Cortex/metabolism , Cerebral Cortex/pathology , Disease Models, Animal , Hippocampus/metabolism , Hippocampus/pathology , Immunohistochemistry , Male , Neurons/metabolism , Organ Specificity , Pyramidal Cells/metabolism , Rats , Rats, Sprague-Dawley , Reverse Transcriptase Polymerase Chain Reaction , Wounds, NonpenetratingABSTRACT
Previous evidence indicates that both chronic alcohol treatment and traumatic brain injury modulate expression of certain neurotrophins and neurotrophin receptors in cortical tissue. However, the combined effects of chronic alcohol and brain trauma on expression of neurotrophins and their receptors have not been investigated. In the present study, we examined the effects of 6 weeks of chronic ethanol administration on lateral fluid percussion (FP) brain injury-induced alterations in expression of mRNAs for the neurotrophin brain-derived neurotrophic factor (BDNF) and its high affinity receptor, trkB, in rat hippocampus. In both the control- (pair-fed isocaloric sucrose) diet and the chronic ethanol-diet groups, unilateral FP brain injury induced a bilateral increase in levels of both BDNF and trkB mRNAs in the dentate gyrus granule cell layer, and of BDNF mRNA in hippocampal region CA3. However, no significant differences in expression were found between the control-diet and ethanol-diet groups, in either the sham-injured or FP-injured animals. These findings suggest that 6 weeks of chronic ethanol administration does not alter the plasticity of hippocampal BDNF/trkB expression in response to experimental brain injury.
Subject(s)
Alcohol-Related Disorders/metabolism , Brain Injuries/metabolism , Brain-Derived Neurotrophic Factor/genetics , Receptor, trkB/genetics , Transcription, Genetic , Alcohol-Related Disorders/complications , Alcohol-Related Disorders/genetics , Animals , Brain Injuries/complications , Brain Injuries/genetics , Ethanol/blood , Gene Expression Regulation , Male , RNA, Messenger/genetics , Rats , Rats, Sprague-Dawley , Time FactorsABSTRACT
This study examined the effects of 3 months of chronic ethanol administration (CEAn) on the behavioral outcome in rats after lateral fluid percussion (FP) brain injury. Rats were given either an ethanol liquid diet (ethanol diet groups) or a pair-fed isocaloric sucrose control diet (control diet groups) for 3 months. Then, rats from both diet groups were subjected to either lateral FP brain injury of moderate severity (1.8 atm) or to sham operation. Postinjury behavioral measurements revealed that brain injury caused significant spatial learning disability in both diet groups. There were no significant differences in spatial learning ability in the sham or brain-injured animals between the control and ethanol diets. However, a trend towards cognitive impairment in the sham animals and a trend towards reduced deficits in the brain-injured animals were observed in the ethanol diet group. Histologic analysis of injured animals from both diet groups revealed similar extents of ipsilateral cortical and hippocampal CA3 damage. These results, in general, suggest that 3 months of CEAn does not significantly alter the behavioral and morphologic outcome of experimental brain injury.
Subject(s)
Alcoholism/complications , Alcoholism/physiopathology , Behavior, Animal/drug effects , Behavior, Animal/physiology , Brain Injuries/physiopathology , Brain/drug effects , Brain/physiopathology , Central Nervous System Depressants/adverse effects , Ethanol/adverse effects , Percussion/adverse effects , Alcohol Drinking/adverse effects , Animals , Body Weight/drug effects , Body Weight/physiology , Brain/pathology , Brain Injuries/pathology , Chronic Disease , Cognition/drug effects , Cognition/physiology , Cognition Disorders/etiology , Cognition Disorders/pathology , Cognition Disorders/physiopathology , Ethanol/analysis , Ethanol/blood , Food, Formulated/adverse effects , Male , Maze Learning/drug effects , Maze Learning/physiology , Rats , Rats, Sprague-Dawley , Time FactorsABSTRACT
This study examined the accumulation of the cytotoxic lipid peroxidation product 4-hydroxynonenal (HNE) after lateral fluid percussion (FP) brain injury in rats. A diffuse distribution of HNE-immunoreactivity (HNE-ir) was observed in the cortex and hippocampus of the ipsilateral, but not of the contralateral, hemisphere at 30 min, 6 h, 24 h, and 48 h after brain injury. The HNE-ir was well-localized in cell bodies of the ipsilateral cortex and the CA3 pyramidal layer in the ipsilateral hippocampus. Because HNE's interaction with certain proteins causes protein dysfunction and HNE, in vitro, causes neuronal cell damage, the present results suggest that HNE's interaction with neuronal proteins may contribute to neuronal damage in the ipsilateral cortex and hippocampus after brain injury.
Subject(s)
Aldehydes/metabolism , Cerebral Cortex/metabolism , Hippocampus/metabolism , Lipid Peroxidation/physiology , Animals , Cerebral Cortex/injuries , Hippocampus/injuries , Immunohistochemistry , Male , Rats , Rats, Sprague-DawleyABSTRACT
The hypothesis that lactate and free fatty acids (FFA) are elevated in the first minutes after subarachnoid hemorrhage (SAH) is tested. Adult rats were subjected to an endovascular SAH through the right internal carotid artery while under anesthesia. The brains were frozen in-situ at 15, 30, 60 min, and 24 h post-hemorrhage. Regional measures of tissue lactic acid and FFA were made in the hippocampi, ipsilateral cortex, contralateral cortex, and cerebellum. Lactic acid levels were significantly elevated from sham animals in each region within the first hour (p<0.0001 cerebellum, right, and contralateral cortex, p<0.01 hippocampus), but did not change significantly over the first hour. At 24 h post-hemorrhage, there was no significant difference in the lactic acid levels from controls. Similarly, total FFA were significantly higher in each region as compared to sham operated controls within the first hour (p<0.001 cerebellum, p<0.05 hippocampus, p<0.05 contralateral cortex, p<0.0001 ipsilateral cortex). By 24 h, there was no significant difference in FFA levels from shams. The data indicate that aerobic metabolism fails and cellular damage with degradation of cell membranes occurs in the first minutes after SAH, and lasts for at least 1 h. However, this process is stabilized within 24 h in our model. Although the largest effect was seen in the ipsilateral cortex, all areas of the brain were effected.
Subject(s)
Brain/metabolism , Fatty Acids, Nonesterified/metabolism , Lactic Acid/metabolism , Subarachnoid Hemorrhage/metabolism , Animals , Male , Rats , Rats, Sprague-Dawley , Tissue DistributionABSTRACT
Regional activities of phosphoinositide-specific phospholipase C (PLC) were measured after lateral fluid percussion (FP) brain injury in rats. The activity of PLC on phosphatidylinositol 4,5-bisphosphate (PIP2) in the rat cortex required calcium, and at 45 microM concentration it increased PLC activity by about ten-fold. The activity of PLC was significantly increased in the cytosol fraction in the injured (left) cortex (IC) at 5 min, 30 min and 120 min after brain injury. However, in the same site, increases were observed in the membrane fraction only at 5 min after brain injury. In both the contralateral (right) cortex (CC) and ipsilateral hippocampus (IH), the activity of PLC was increased in the cytosol only at 5 min after brain injury. These results suggest that increased activity of PLC may contribute to increases in levels of cellular diacylglycerol and inositol trisphosphate in the IC (the greatest site of injury), and to a smaller extent in the IH and CC, after lateral FP brain injury. It is likely that this increased PLC activity is caused by alteration in either the levels or activities of one or more of its isozymes (PLCbeta, PLCgamma, and PLCdelta) after FP brain injury.
Subject(s)
Brain Injuries/enzymology , Type C Phospholipases/metabolism , Animals , Male , Phosphatidylinositol 4,5-Diphosphate/metabolism , Phosphatidylinositol Diacylglycerol-Lyase , Rats , Rats, Sprague-DawleyABSTRACT
Lactate and free fatty acids (FFAs) were extracted from the cortices and hippocampi of rats subjected to sham operation, or mild (1.25 atm) or moderate (2.0 atm) fluid percussion (FP) injury, and their total tissue concentrations were measured. The elevation of lactate in the injured left cortex (IC) and ipsilateral hippocampus (IH) was significantly greater in the moderate-injury than in the mild-injury group at most test times between 5 min and 48 h after injury. Levels of total FFAs were elevated in the IC and IH to a greater extent and for a longer period after injury in the moderate-injury (up to 48 h) than in the mild-injury group (up to 20 min). In general, the extent and duration of the elevation of most of the individual FFAs (palmitic, stearic, oleic, and arachidonic acids) in the IC and IH were also greater in the moderate-injury group than in the mild-injury group. In the contralateral cortex (CC) and hippocampus (CH), the elevation of lactate and total FFAs (and individual stearic and arachidonic acids) were also greater in the moderate-injury group than in the low-injury group at 5 min after injury. The extravasation of Evans blue in the IC and IH from 3 to 6 h after injury was also the greatest in the moderate-injury group. The hippocampal CA3 neuronal cell loss, but not cortical lesion volume, also increased with the severity of injury. These findings suggest that certain neurochemical, physiological (blood-brain barrier permeability), and morphologic responses increase with the severity of FP brain injury, and such relationships are consistent with the increased behavioral deficits observed with the increase of severity of brain injury.
Subject(s)
Blood-Brain Barrier/physiology , Cerebral Cortex/injuries , Extravasation of Diagnostic and Therapeutic Materials/etiology , Fatty Acids, Nonesterified/metabolism , Hippocampus/injuries , Lactic Acid/metabolism , Analysis of Variance , Animals , Cerebral Cortex/metabolism , Cerebral Cortex/pathology , Cerebral Cortex/physiopathology , Coloring Agents , Disease Models, Animal , Disease Progression , Evans Blue , Hippocampus/metabolism , Hippocampus/pathology , Hippocampus/physiopathology , Male , Rats , Rats, Sprague-Dawley , Time Factors , Trauma Severity IndicesABSTRACT
Recent studies have suggested that brain-derived neurotrophic factor (BNDF) and its receptor, trkB, may provide neuroprotection following injury to the central nervous system. Conversely, other studies have implicated BDNF as a contributing factor to neurodegenerative events that occur following injury. In order to further investigate the role of BDNF in neuroprotection, we subjected adult rats to a lateral fluid percussion (FP) injury of moderate severity (2.0-2.1 atm) or sham injury. After survival periods of 1, 3, 6, 24, or 72 h, the brains were processed for the in situ hybridization localization of BDNF and trkB mRNAs using 35S-labeled cRNA probes. Hybridization levels were compared between injured and sham animals for regions of the cortex that were located within, adjacent to, and remote from the site of the cortical contusion. BDNF mRNA levels were significantly decreased in the injured cortex at 72 h, increased in adjacent cortical areas at 3 h, and increased bilaterally in the piriform cortex from 3 to 24 h post-FP injury. Expression of trkB mRNA was significantly decreased at all postinjury time-points in the injured cortex and at 24 h in the adjacent cortex. These results demonstrate that, following lateral FP injury, BDNF and trkB mRNA levels are decreased in cortical regions that contain degenerating neurons, generally unchanged in adjacent regions, and increased in remote areas. Thus, injury-induced decreases in the expression of BDNF and trkB may confer vulnerability to neurons within the cortical contusion.
Subject(s)
Brain Injuries/metabolism , Brain-Derived Neurotrophic Factor/metabolism , Cerebral Cortex/metabolism , RNA, Messenger/metabolism , Receptor, trkB/metabolism , Animals , Autoradiography , Cerebral Cortex/injuries , Disease Models, Animal , Gene Expression Regulation , In Situ Hybridization , Male , Rats , Rats, Sprague-Dawley , Time FactorsABSTRACT
This study examined the effects of the administration of kynurenate, a non-specific excitatory amino acid (EAA) receptor subtype antagonist, on the regional accumulation of diacylglycerol (DG) and free fatty acids (FFAs) after lateral fluid percussion (FP) brain injury in the rat. After brain injury of moderate severity (2.0 atm), rats were treated with either kynurenate (200 mg/kg, i.v.) or saline at 5 min after injury. In the saline-treated brain-injured rats, levels of all individual DG-fatty acids (palmitic, stearic, oleic and arachidonic acids) and total DG-fatty acids were increased in the ipsilateral left cortex and hippocampus at 30 min and 60 min after injury. Kynurenate administration attenuated increases of individual and total DG-fatty acids in the ipsilateral cortex at 30 and 60 min and in the ipsilateral hippocampus at 30 min after FP brain injury. At 30 and 60 min after FP brain injury, increases in the levels of individual FFAs (palmitic, stearic, oleic and arachidonic acids) and of total FFAs were also observed in the ipsilateral cortex and hippocampus of the saline-treated injured rats. Kynurenate administration attenuated increases of all individual and total FFAs in the ipsilateral cortex and hippocampus either at 30 min alone or at both 30 min and 60 min after FP brain injury. In the contralateral cortex, levels of both DG-fatty acids and FFAs were not increased in the saline-treated injured rats and were also not affected by the administration of kynurenate. These results support the role of EAA receptor subtypes in the phospholipases-catalyzed formation of DG and FFAs in the ipsilateral cortex and hippocampus after lateral FP brain injury.
Subject(s)
Brain Injuries/drug therapy , Diglycerides/metabolism , Excitatory Amino Acid Antagonists/therapeutic use , Fatty Acids, Nonesterified/metabolism , Kynurenic Acid/therapeutic use , Analysis of Variance , Animals , Brain Injuries/etiology , Brain Injuries/metabolism , Drug Evaluation, Preclinical , Male , Phospholipids/metabolism , Rats , Rats, Sprague-DawleyABSTRACT
This study examined the effects of 6 weeks of chronic ethanol administration on the behavioral outcome in rats after lateral fluid percussion (FP) brain injury. Rats were given either an ethanol liquid diet (ethanol diet-groups) or a pair-fed isocaloric sucrose control diet (control diet groups) for 6 weeks. After 6 weeks, the ethanol diet was discontinued for the ethanol diet rats and they were then given the control sucrose diet for 2 days. During those 2 days, the rats were trained to perform a beam-walking task and subjected to either lateral FP brain injury of low to moderate severity (1.8 atm) or to sham operation. In both the control diet and the ethanol diet groups, lateral FP brain injury caused beam-walking impairment on days 1 and 2 and spatial learning disability on days 7 and 8 after brain injury. There were no significant differences in beam-walking performance and spatial learning disability between brain injured animals from the control and ethanol diet groups. However, a trend towards greater behavioral deficits was observed in brain injured animals in the ethanol diet group. Histologic analysis of both diet groups after behavioral assessment revealed comparable ipsilateral cortical damage and observable CA3 neuronal loss in the ipsilateral hippocampus. These results only suggest that chronic ethanol administration, longer than six weeks of administration, may worsen behavioral outcome following lateral FP brain injury. For more significant behavioral and/or morphological change to occur, we would suggest that the duration of chronic ethanol administration must be increased.
Subject(s)
Behavior, Animal/physiology , Brain Injuries/psychology , Central Nervous System Depressants/pharmacology , Ethanol/pharmacology , Animals , Behavior, Animal/drug effects , Body Weight/drug effects , Brain/pathology , Brain Injuries/pathology , Diet , Dietary Sucrose/pharmacology , Functional Laterality/physiology , Male , Maze Learning/drug effects , Postural Balance/drug effects , Rats , Rats, Sprague-DawleyABSTRACT
This study examined the effects of the administration of D-amphetamine on the regional accumulation of lactate and free fatty acids (FFAs) after lateral fluid percussion (FP) brain injury in the rat. Rats were subjected to either FP brain injury of moderate severity (1.9 to 2.0 atm) or sham operation. At 5 min after injury, rats were treated with either d-amphetamine (4 mg/kg, i.p.) or saline. At 30 min and 60 min after brain injury, brains were frozen in situ, and cortices and hippocampi were excised at 0 degrees C. In the saline-treated brain injured rats, levels of lactate were increased in the ipsilateral left cortex and hippocampus at 30 min and 60 min after injury. These increases were attenuated by the administration of D-amphetamine at 5 min after lateral FP brain injury. At 30 and 60 min after FP brain injury, increases in the levels of all individual FFAs (palmitic, stearic, oleic and arachidonic acids) and of total FFAs were also observed in the ipsilateral cortex of the saline-treated injured rats. These increases in the ipsilateral cortex and hippocampus were also attenuated by the administration of d-amphetamine. Neither levels of lactate nor levels of FFAs were increased in the contralateral cortex in the saline-treated injured rats at 30 min or 60 min after FP brain injury. The levels of lactate and FFAs in the contralateral cortex were also unaffected by the administration of D-amphetamine. These results suggest that the attenuation of increases in the levels of lactate and FFAs in the ipsilateral cortex and hippocampus may be involved in the amphetamine-induced improvement in behavioral outcome after lateral FP brain injury.
Subject(s)
Brain Chemistry/physiology , Brain Injuries/drug therapy , Brain Injuries/metabolism , Central Nervous System Stimulants/therapeutic use , Dextroamphetamine/therapeutic use , Animals , Brain Chemistry/drug effects , Fatty Acids, Nonesterified/blood , Freezing , Lactic Acid/blood , Male , Rats , Rats, Sprague-DawleyABSTRACT
Levels of PLCgamma, a phospholipase C (PLC) isozyme, were significantly increased in the cytosol in the injured left cortex (LC) at 5, 30 and 120 min after brain injury. In the same site, although levels of membrane PLCgamma did not alter at 5 and 30 min, they were found to be decreased at 2 h after brain injury. In general, the levels of both cytosolic and membrane PLCgamma were unaltered in the contralateral right cortex (RC), ipsilateral left hippocampus (LH) and contralateral right hippocampus (RH) between 5 and 120 min after brain injury. These results suggest that, in addition to well-proposed excitatory neurotransmitter-receptor systems, increased levels of PLCgamma may also contribute to alterations in PIP2 signal transduction pathway, particularly in the greatest injury site (LC) after lateral FP brain injury.
Subject(s)
Brain Injuries/enzymology , Brain/enzymology , Isoenzymes/metabolism , Type C Phospholipases/metabolism , Animals , Cell Membrane/enzymology , Cerebral Cortex/enzymology , Cytosol/enzymology , Functional Laterality , Hippocampus/enzymology , Male , Organ Specificity , Percussion , Phospholipase C gamma , Rats , Rats, Sprague-Dawley , Reference Values , Time FactorsABSTRACT
Recent investigations have shown that expression of mRNAs for the neurotrophins brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) is differentially altered in the hippocampus following traumatic brain injury. In the present study, modulation of neurotrophin receptor expression was examined in the hippocampus in a rat model of traumatic brain injury using in situ hybridization. Messenger RNA for trkB, the high-affinity receptor for BDNF and neurotrophin-4 (NT-4), was increased between 3 and 6 h bilaterally in the dentate gyrus following a lateral fluid-percussion brain injury of moderate severity (2.0-2.1 atm). No time-dependent alterations were observed for trkB mRNA in hippocampal subfields CA1 and CA3. Levels of mRNA for trkC, the high-affinity receptor for NT-3, did not change in any region of the hippocampus. These data demonstrate that lateral fluid-percussion injury modulates expression of trkB mRNA in the hippocampus and support a role for BDNF/trkB signalling mechanisms in secondary events associated with traumatic brain injury.
Subject(s)
Dentate Gyrus/injuries , Dentate Gyrus/metabolism , Neuroprotective Agents/metabolism , Receptor Protein-Tyrosine Kinases/genetics , Receptors, Nerve Growth Factor/genetics , Animals , Dentate Gyrus/chemistry , Disease Models, Animal , In Situ Hybridization , Male , Neuronal Plasticity/physiology , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Receptor, Ciliary Neurotrophic FactorABSTRACT
Previous studies have suggested that the neurotrophins brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) are neuroprotective or neurotrophic for certain subpopulations of hippocampal neurons following various brain insults. In the present study, the expression of BDNF and NT-3 mRNAs in rat hippocampus was examined after traumatic brain injury. Following lateral fluid percussion (FP) brain injury of moderate severity (2.0-2.1 atm) or sham injury, the hippocampi from adult rats were processed for the in situ hybridization localization of BDNF and NT-3 mRNAs using 35S-labeled cRNA probes at post-injury survival times of 1, 3, 6, 24 and 72 h. Unilateral FP injury markedly increased hybridization for BDNF mRNA in the dentate gyrus bilaterally which peaked at 3 h and remained above control levels for up to 72 h post-injury. A moderate increase in BDNF mRNA expression was also observed bilaterally in the CA3 region of the hippocampus at 1, 3, and 6 h after FP injury, but expression declined to control levels by 24 h. Conversely, NT-3 mRNA was significantly decreased in the dentate gyrus following FP injury at the 6 and 24 h survival times. These results demonstrate that FP brain injury differentially modulates expression of BDNF and NT-3 mRNAs in the hippocampus, and suggest that neurotrophin plasticity is a functional response of hippocampal neurons to brain trauma.
Subject(s)
Brain Injuries/metabolism , Brain-Derived Neurotrophic Factor/genetics , Hippocampus/metabolism , Nerve Growth Factors/genetics , RNA, Messenger/metabolism , Animals , Brain Injuries/etiology , Dentate Gyrus/metabolism , Hippocampus/injuries , Male , Neuronal Plasticity/physiology , Neurotrophin 3 , Rats , Rats, Sprague-DawleyABSTRACT
Regional levels of lactate and free fatty acids (FFA) were measured after lateral fluid percussion (FP) brain injury in rats. At 5 min after injury, tissue concentrations of lactate were elevated in the cortices and hippocampi of both ipsilateral and contralateral hemispheres. Whereas lactate levels had returned to normal by about 20 min after injury in the penumbra and contralateral cortices, their elevation persisted in the ipsilateral injured cortex and hippocampus for 24 h after injury. Increases in the levels of FFA (particularly stearic and arachidonic acids) were observed in the cortices and hippocampi of both ipsilateral and contralateral hemispheres at 5 min after injury; these levels returned to normal in only the penumbra and contralateral cortices by 20 min after injury. Increased amounts of palmitic and oleic acids were also found only in the injured left cortex and ipsilateral hippocampus at 20 min or later after injury. In general, these elevations persisted for as long as 6 to 24 h in the injured cortex and for 2.5 to 24 h after injury in the ipsilateral hippocampus. Histologic studies revealed a similar extent of damage in the cortex between 5 min and 24 h after injury, whereas damage in the CA3 region of the ipsilateral hippocampus increased during that period. These findings suggest a role for lactic acid and FFA, two secondary injury factors, in neuronal cell loss after brain injury.
Subject(s)
Brain Injuries/metabolism , Brain Injuries/pathology , Cerebral Cortex/metabolism , Fatty Acids, Nonesterified/metabolism , Hippocampus/metabolism , Lactates/metabolism , Animals , Arachidonic Acid/metabolism , Cerebral Cortex/pathology , Functional Laterality , Hippocampus/pathology , Male , Neurons/metabolism , Neurons/pathology , Oleic Acid/metabolism , Palmitic Acid/metabolism , Pyramidal Cells/pathology , Rats , Rats, Sprague-Dawley , Stearic Acids/metabolism , Time FactorsABSTRACT
This study examined the delayed effects of the administration of d-amphetamine, methoxamine (an alpha1-adrenergic receptor agonist), and prazosin (an alpha1-adrenergic receptor antagonist) on the behavioral outcome of lateral fluid-percussion (FP) brain injury. Rats trained to perform a beam-walking task were subjected to brain injury of moderate severity (2.1 to 2.2 atm). Twenty-four hours after injury, rats were treated with amphetamine, methoxamine, or prazosin at two or three different dose levels. Amphetamine-treated animals displayed no significant improvement in beam-walking ability either during or after drug intoxication (from days 3 to 5 after brain injury). Similarly, neither methoxamine nor prazosin significantly affected beam-walking ability during or after drug intoxication. Neither amphetamine treatment at three different doses nor treatment with methoxamine or prazosin at two different doses affected the spatial learning disabilities of brain-injured animals. These results suggest that (1) unlike amphetamine administration after sensorimotor cortex (SMC) ablation or contusion brain injury models, amphetamine administration at 24 h after concussive FP brain injury does not improve beam-walking performance; (2) unlike amphetamine administration 10 min after concussive FP brain injury amphetamine administration 24 h after injury does not improve cognitive function; and (3) unlike prazosin administration after SMC ablation brain injury, prazosin administration 24 h after concussive FP brain injury does not effect beam-walking performance.
Subject(s)
Amphetamine/therapeutic use , Behavior, Animal/drug effects , Brain Injuries/drug therapy , Methoxamine/therapeutic use , Prazosin/therapeutic use , Animals , Male , Rats , Rats, Sprague-DawleyABSTRACT
The effects of 6 weeks of chronic ethanol administration on the lateral fluid percussion (FP) brain injury-induced regional accumulation of lactate and on the levels of total high-energy phosphates were examined in rats. In both the chronic ethanol diet (ethanol diet) and pair-fed isocaloric sucrose control diet (control diet) groups, tissue concentrations of lactate were elevated in the cortices and hippocampi of both the ipsilateral and contralateral hemispheres at 5 min after brain injury. In both diet groups, concentrations of lactate were elevated only in the injured left cortex and the ipsilateral hippocampus at 20 min after FP brain injury. No significant differences were found in the levels of lactate in the cortices and hippocampi of sham animals and brain-injured animals between the ethanol and control diet groups at 5 min and 20 min after injury. In the ethanol and control diet groups, tissue concentrations of total high-energy phosphates (ATP + PCr) were not affected in the cortices and hippocampi at 5 min and 20 min after lateral FP brain injury. No significant differences were found in the levels of total high-energy phosphates in the cortices and hippocampi of the sham and brain-injured animals between the ethanol and control diet groups at 5 min and 20 min after injury. Histologic studies revealed a similar extent of damage in the cortex and in the CA3 region of the ipsilateral hippocampus in both diet groups at 14 days after lateral FP brain injury. These findings suggest that 6 weeks of chronic ethanol administration does not alter brain injury-induced accumulation of lactate, levels of total high energy phosphates, and extent of morphological damage.
Subject(s)
Adenosine Triphosphate/metabolism , Brain Injuries/metabolism , Central Nervous System Depressants/pharmacology , Ethanol/pharmacology , Lactic Acid/metabolism , Phosphocreatine/metabolism , Animals , Body Weight/drug effects , Brain/pathology , Brain Injuries/blood , Brain Injuries/pathology , Central Nervous System Depressants/blood , Ethanol/blood , Male , Rats , Rats, Sprague-DawleyABSTRACT
Regional concentrations of leukotriene C4 and extravasation of Evans blue were measured after lateral fluid-percussion brain injury in rats. Tissue levels of LTC4 were elevated in the injured cortex at 10 min, 30 min, and 1 h after injury; these levels returned to normal by 2 h after injury. Increases in the levels of LTC4 were also observed in the ipsilateral hippocampus after brain injury, and these elevations persisted for 2 h after injury. No significant increase in levels of LTC4 was observed in the contralateral cortex at any time after injury. A substantial extravasation of Evans blue was observed only in the ipsilateral cortex and hippocampus at 3 h and 6 h after brain injury. Although a temporal association between LTC4 and blood-brain barrier (BBB) breakdown is suggested by these data, no cause-and-effect relationship has been addressed in this study. However, it is possible that, as is true for cerebral ischemia, LTC4 may play a role as a mediator in the BBB breakdown associated with fluid-percussion brain injury in rats.