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Fluid percussion brain injury in the developing and adult rat: a comparative study of mortality, morphology, intracranial pressure and mean arterial blood pressure.

Changes in intracranial pressure (ICP) and mean arterial blood pressure (MABP) were measured for 30 min following an experimental fluid percussion traumatic brain injury in postnatal day 17 (P17), P28 and adult rats. Under enflurane anesthesia the left femoral artery was cannulated for MABP measurements and a 20 gauge needle was stereotaxically positioned into the right lateral ventricle for ICP measurements. Three different injury severities (mild: 1.35-1.45 atm, moderate: 2.65-2.75 atm, severe: 3.65-3.75 atm) were delivered over the left parietal cortex to each of the age groups. The biomechanical/physiological results indicated that fluid percussion generated reproducible traumatic brain injuries in the developing rat. Furthermore, with increasing injury severity the physiological responses (in terms of ICP and MABP) became more pronounced, resulting in a corresponding increase in mortality (mild, moderate, severe, respectively, P17: 27%, 36%, 100%; P28: 33%, 30%, 75%; adult: 0%, 20%, 55%). Compared to adult animals, developing rats exhibited pronounced hypotension in response to closed head injury, which most likely explains the greater percent mortality among the younger animals. The utilization of this model will allow for future studies addressing the consequences of traumatic brain injury when it is sustained early in development.

Analysis of Variance↗

Efficacy and safety of intrapulmonary percussive ventilation superimposed on conventional ventilation in obese patients with compression atelectasis.

PURPOSE: To investigate the efficacy and safety of intrapulmonary percussive ventilation (IPV) in obese patients, we assessed their respiratory and hemodynamic functions during IPV superimposed on conventional ventilation. MATERIALS AND METHODS: Ten obese patients with acute respiratory failure due to compression atelectasis who had not improved by conventional ventilation were treated with IPV. Hemodynamic parameters, ventilator settings, and intracranial pressure (n = 1) were recorded every hour. Arterial blood gas was analyzed every 3 hours. The efficacy and safety of IPV was assessed at the start of weaning. RESULTS: Before IPV, Pao(2)/Fio(2) ratio remained low (189 +/- 63 mm Hg), which significantly increased to 243 +/- 67 mm Hg at 3 hours from the initiation of IPV (P < .01). Furthermore, it continuously increased to 280 +/- 50 mm Hg at 24 hours (P < .01). Intrapulmonary percussive ventilation induced significant increase in dynamic compliance from control value of 30 +/- 8 mL/cm H(2)O at 0 hours to 35 +/- 9 mL/cm H(2)O at 12 hours (P < .05) and to 38 +/- 8 mL/cm H(2)O at 24 hours (P < .01). Heart rate and mean arterial pressure were not significantly changed during IPV. Improvement of compression atelectasis was confirmed by their chest computed tomographic scans. Adverse effects such as pneumothorax and intracranial hypertension were not seen. CONCLUSIONS: These results demonstrated that IPV was effective and safe in improving compression atelectasis without adverse effects in obese patients.

Adult↗

New estimates of tooth mark and percussion mark frequencies at the FLK Zinj site: the carnivore-hominid-carnivore hypothesis falsified.

Traditional interpretations of hominid carcass acquisition strategies revolve around the debate over whether early hominids hunted or scavenged. A popular version of the scavenging scenario is the carnivore-hominid-carnivore hypothesis, which argues that hominids acquired animal resources primarily through passive opportunistic scavenging from felid-defleshed carcasses. Its main empirical support comes from the analysis of tooth mark frequency and distribution at the FLK Zinj site reported by Blumenschine (Blumenschine, 1995, J. Hum. Evol. 29, 21-51), in which it was shown that long bone mid-shafts exhibited a high frequency of tooth marks, only explainable if felids had preceded hominids in carcass defleshing. The present work shows that previous estimates of tooth marks on the FLK Zinj assemblage were artificially high, since natural biochemical marks were mistaken for tooth marks. Revised estimates are similar to those obtained in experiments in which hyenas intervene after humans in bone modification. Furthermore, analyses of percussion marks, notches, and breakage patterns provide data which are best interpreted as the results of hominid activity (hammerstone percussion and marrow extraction), based on experimentally-derived referential frameworks. These multiple lines of evidence support previous analyses of cut marks and their anatomical distribution; all indicate that hominids had early access to fleshed carcasses that were transported, processed, and accumulated at the FLK Zinj site.

Animals↗

High frequency percussive ventilation in burn patients: hemodynamics and gas exchange.

High frequency percussive ventilation (HFPV) is a recent ventilatory mode, which combines conventional cycles with high frequency percussions. HFPV was initially instituted as salvage therapy after acute respiratory failure following smoke inhalation injury achieving in each case a dramatic improvement of blood oxygenation, PaCO(2) and ventilatory pressures. This study investigates the influence of HFPV on hesmodynamics, blood oxygenation and ventilatory parameters in eight stable ICU burn patients requiring artificial ventilatory support during a postoperative period following traumatic injury. Periods of 2h were analysed receiving conventional ventilation and HFPV with a high frequency of 400 and 800 cycles/min. Hemodynamic data were not significantly modified; peak inspiratory pressure was significantly lower under HFPV but mean airway pressure was unchanged. Blood oxygenation and CO(2) elimination were significantly improved under HFPV. No side effects were noted. These observations suggest that HFPV could improve pulmonary gas exchanges under lower peak pressures and without hemodynamic compromise. HFPV could represent an interesting alternative open lung strategy method to improve alveolar recruitment.

Adult↗

The effect of combined fluid percussion and entorhinal cortical lesions on long-term potentiation.

Among the pathological processes initiated by traumatic brain injury are excessive neuroexcitation and target cell deafferentation. The current study examines the contribution of these injury components, separately as well as their combined effect, on postinjury alterations in the capacity for long-term potentiation and the immunolocalization of N-methyl-D-aspartate receptors and GABA. Adult rats underwent central fluid percussion traumatic brain injury, electrolytic bilateral entorhinal cortex lesions, or a combined injury of both procedures separated by 24 h. At two or 15 days postinjury, the capacity for long-term potentiation of the Schaffer collateral-commissural input to CA1 was measured in acute electrophysiological recordings. Entorhinal cortical lesions resulted in time-dependent increases in the effectiveness of tetanic stimulation to elevate population postsynaptic potentials and population spike amplitudes. These lesions also resulted in a marked intensification in the density of N-methyl-D-aspartate receptors in the CA1 stratum lacunosum-moleculare. All injury conditions that included fluid percussion as a component (alone or in combined injuries) produced a persistent impairment in long-term potentiation of the evoked population postsynaptic potentials. Thus, in combined injuries, the presence of concussion-induced neuroexcitation attenuated deafferentation-induced response increases. Both N-methyl-D-aspartate receptor and GABA immunobinding following combined injuries were also reduced relative to those observed following entorhinal lesions alone. The present results suggest that a process of receptor plasticity, possibly involving reactive synaptogenesis, may contribute to postdeafferentation enhancements of long-term potentiation, and that a traumatic brain insult will attenuate these enhancements. This interaction of different injury components suggests that recovery of function following brain injury may be enhanced by pharmacological reduction of neuroexcitation during postinjury intervals of reactive receptor plasticity.

Animals↗

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↗

[Intrapulmonary percussion in cystic fibrosis].

Endobronchial percussion was performed in eight cystic fibrosis patients of 15 to 26 years of age using a high-frequency ventilator system. Lung function changes and blood gas parameters were examined. The method resulted in an improved FEV1 (P less than 0.025) and in blood gas improvements such as pO2, base excess (P less than 0.001) and oxygen saturation (P less than 0.001). Endobronchial percussion offers the advantage of being largely independent of patient cooperation in chronic obstructive lung disease such as cystic fibrosis. The decision in favour of long-term treatment depends in each case on the individual acceptance by the patient.

Adolescent↗

Selective loss of timbre perception for keyboard and percussion instruments following a right temporal lesion.

We report the case of a 65-year-old man WDK, who experienced selective loss of timbre perception for keyboard and percussion instruments following a right temporal stroke comprising the anterior superior and medial gyrus and parts of the insular region. Formerly an avid listener to music, the sound of an orchestra appeared to be "flat" to him. WDK and a matched control subject underwent a detailed neuropsychological test battery covering basic auditory function (audiometry and just notable difference for pitch shifts), specific auditory function (recognition of environmental sounds), specific musical functions like discrimination of pitch, interval, contour, rhythm and metre, recognition of familiar melodies, emotional responsiveness, perception of timbre and auditory spectral analysis. While WDK displayed no deficits in primary auditory function, the test battery revealed a selective impairment in the perception of timbre of keyboard and percussion instruments which could be traced to a deficit in discriminating rapid changes of the spectral composition of a tone. Hence, these findings demonstrate the existence of highly specific neural networks underlying isolated aspects of timbre perception in the right anterior temporal lobe.

Acoustic Stimulation↗

Craniectomy position affects morris water maze performance and hippocampal cell loss after parasagittal fluid percussion.

Valid and reliable animal models are essential for mechanistic and therapeutic studies of traumatic brain injury (TBI). Therefore, model characterization is a continual and reciprocal process between the experimental laboratory and the clinic. Several excellent experimental models of TBI, including the lateral fluid percussion rat model, are currently in wide use in many neurotrauma laboratories. However, small differences in the position of lateral fluid percussion craniectomy are reported between labs. Additionally, differences in hippocampal cell death have also been reported. Therefore, we hypothesized that small changes in craniectomy position could affect commonly used outcome measures such as vestibulomotor function, Morris water maze (MWM) performance, hippocampal cell loss, and glial fibrillary acidic protein (GFAP) immunoreactivity. Four placements were systematically manipulated: rostral, caudal, medial, and lateral. The medial and caudal placements produced significantly greater impairments in the MWM acquisition task over the lateral and rostral placements. The rostral placement produced diffuse cortical damage but little hippocampal cell loss. In contrast, the medial, lateral, and caudal placements produced more mid-dorsally localized cortical damage and significant cell loss in the CA2/CA3 and hilus ipsilateral to the injury site. Furthermore, reactive astrocytosis was more pronounced in the medial, lateral, and caudal placements than in the rostral placement. All craniectomy position groups had similar durations of traumatic unconsciousness and similar impairment on motor tasks. We conclude that small alterations in craniectomy position produce differences in cognitive performance, hippocampal cell loss, and reactive astrocytosis but not in motor performance nor transient unconsciousness.

Animals↗

Brain levels of polyethylene glycol-conjugated superoxide dismutase following fluid percussion brain injury in rats.

Polyethylene glycol-conjugated superoxide dismutase (PEG-SOD) is being explored as an agent to reduce oxygen radical-mediated damage following brain injury. Yet little is known concerning the site of action of IV-administered PEG-SOD or the capacity of this conjugated enzyme to enter the brain. The purpose of this study was to determine the brain content of PEG-SOD in normal and fluid percussion injured rats. The fluid percussion device was attached over the right parietal cortex and a moderate (2.0 atm) intensity injury was produced. PEG-SOD was conjugated with 125I and given (2000 U/kg, 5 microCi/kg) to rats either 30 min before or 30 min after brain injury. Another group received [125I]PEG-SOD but was not injured. Plasma and left and right brain hemispheres were counted for [125I]PEG-SOD. Plasma levels of [125I]PEG-SOD declined similarly in all three groups during the 90-min period after IV administration. Brain [125I]PEG-SOD was low in control animals (0.034 U/g wet wt). In animals given PEG-SOD after injury the brain level was elevated sixfold in both the left and right hemispheres, compared to control. In rats given the drug before injury, [125I]PEG-SOD was 10 times control level in the right hemisphere, which is the side on which the injury device is attached, and 6 times control level in the left hemisphere. We conclude that traumatic brain injury produces an increase in brain PEG-SOD. The exact cellular site of the increased brain PEG-SOD remains to be clarified.

Animals↗

Early assessment of neurologic deficits in the fluid percussion model of brain injury.

This study was designed to quantify the early neurologic effects of brain injury elicited by fluid percussion to the dura of cats. Propofol was used for surgical anesthesia because recovery in normal animals from an intravenous infusion was found to be nearly complete within 2 h of cessation and absolutely complete by 4 h. In addition, a cat coma scale (CCS) was developed that reflects normal (CCS, 14) to moribund (CCS, 3) behavior. The CCS values at 6 h were compared with the force of injury expressed in atmospheres (atm), maximum blood pressure change, and gross neuropathology to ascertain which parameter might best account for the behavior observed after brain injury. The results showed that decreasing neurologic scores correlated well with increasing atmospheres of injury (Pearson's r 0.71, p < 0.001) but not with the rise in systolic blood pressure caused by the trauma (n = 29). Coma scores did correlate with the cross sectional area of ponto-mesencephalic lesions (Pearson's r = 0.51, p < 0.01) and proved to be significantly different in animals grouped according to lesion size of less or more than 3 mm in length (t test, p < 0.01). Thus the CCS and the pharmacologic properties of propofol permit an early analysis of the neurologic status in the feline fluid percussion model of brain injury. These procedures could facilitate the evaluation of early biochemical changes that affect behavior and of therapies designed to ameliorate the deleterious effects of head injury.

Anesthesia↗

Fetal hippocampal transplants attenuate CA3 pyramidal cell death resulting from fluid percussion brain injury in the rat.

Transplantation of fetal neural tissue has been demonstrated to prevent neuronal loss in a number of CNS injury models including spinal cord contusion. However, no studies have examined the neuroprotective role of fetal transplants in models of traumatic brain injury. The present study examined the ability of fetal neural grafts to attenuate neuronal loss resulting from lateral fluid percussion (FP) brain injury in the rat. Lateral FP in the rat elicits a focal contusion within the parietal/temporal cortex and induces cell death in a subset of hippocampal CA3 pyramidal neurons. To examine potential neuroprotective effects of fetal neural grafts, either E16 fetal hippocampus, E16 fetal cortex, or sterile lactated Ringers was stereotaxically transplanted directly into contused cortex 2 days after FP brain injury. The effects of fetal transplants upon adjacent injured hippocampal CA3 regions were then assessed at 4 weeks after grafting utilizing quantitative image analysis. Both fetal cortex and hippocampal grafts survived within contused cortex. Fetal hippocampal grafts significantly attenuated CA3 cell death resulting from lateral fluid percussion, while fetal cortical transplants induced a small, but nonsignificant, amelioration of CA3 pyramidal loss. Thus, neuroprotection by fetal grafts appeared to be tissue specific with hippocampal, but not cortical, fetal transplants significantly reducing posttraumatic CA3 loss. In summary, fetal neural transplantation can ameliorate hippocampal cell death following experimental brain injury.

Animals↗

Posttreatment with intravenous basic fibroblast growth factor reduces histopathological damage following fluid-percussion brain injury in rats.

The purpose of this study was to determine whether treatment with intravenous basic fibroblast growth factor (bFGF) would protect histopathologically in a rat model of traumatic brain injury (TBI). Twenty-four hours prior to TBI, the fluid-percussion interface was positioned parasagittally over the right cerebral cortex. On the second day, fasted rats were anesthetized with 70% nitrous oxide, 1% halothane, and 30% oxygen. Under controlled physiological conditions and normothermic brain temperature (37-37.5 degrees C), rats were injured with a fluid-percussion pulse ranging from 1.6 to 1.9 atm. Rats were randomized into two groups where either bFGF (45 micrograms/kg/h) in vehicle (n = 7) or vehicle alone (n = 7) was infused intravenously for 3 h, beginning 30 min after TBI. Three days later, brains were perfusion-fixed for histopathological assessment and quantitative analysis of contusion volume and numbers of necrotic cortical neurons. In vehicle-treated animals, necrotic neurons were observed throughout the lateral cerebral cortex remote from the impact site. In addition, an intracerebral contusion was present in all rats at the gray-white interface underlying the injured cortical areas. Posttraumatic administration of bFGF significantly reduced the numbers of damaged cortical neuron profiles at several coronal levels and reduced the total number of damaged neurons (696 +/- 148 vs. 1,248 +/- 198, means +/- SEM), p < 0.05, ANOVA). In addition, contusion ares at several coronal levels as well as total contusion volume was significantly reduced (1.13 +/- 0.39 mm(3) vs. 3.18 +/- 0.81 mm(3), p < 0.05). These data demonstrate neuroprotection with intravenous bFGF infusion in the posttraumatic setting.

Animals↗

Time course for recovery of water maze performance and central cholinergic innervation after fluid percussion injury.

This study further investigates the possible connection between postconcussive cognitive impairment and damage to forebrain cholinergic innervation. Moderate parasagittal fluid percussion injury was delivered to adult male rats. Water maze performance and synaptosomal choline uptake was measured at various times following injury. Water maze learning was severely impaired between 1 and 5 weeks, but recovered to normal by 10 weeks. Synaptosomal choline uptake was significantly decreased by 15-27% in the ipsilateral hippocampus and parietal cortex 3 and 7 days following injury, but not by 3 weeks or thereafter. Choline acetyltransferase was also significantly decreased in the ipsilateral cortex at 3 and 7 days with subsequent recovery. This study shows that parasagittal fluid percussion injury causes significant impairment in water maze learning and ipsilateral forebrain cholinergic innervation. Both of these parameters recover spontaneously, but with different time courses.

Animals↗

Posttreatment with high-dose albumin reduces histopathological damage and improves neurological deficit following fluid percussion brain injury in rats.

We have recently shown that high-dose human serum albumin (HSA) therapy confers marked histological protection in experimental middle cerebral artery occlusion. Thus, the purpose of this study was to determine whether treatment with high-dose HSA would protect in a rat model of traumatic brain injury (TBI). Twenty-four hours prior to TBI, the fluid percussion interface was positioned parasagittally over the right cerebral cortex. On the following day, fasted rats were anesthetized with 3% halothane, 70% nitrous oxide, and 30% oxygen and received right parieto-occipital parasagittal fluid-percussion injury (1.5-2.0 atm). Cranial and rectal temperatures were monitored throughout the experiment and held at normothermic levels (36.5-37.5 degrees C) by a warming lamp above the animal's head. The agent (25% human serum albumin, HSA) or vehicle (sodium chloride 0.9%) was administered i.v. (1% of body weight) 15 min after trauma. Behavioral function was evaluated in all rats before and after TBI (at 2 h, 24 h, 48 h, 72 h, and 7 days). Neurological function was graded on a scale of 0-12 (normal score = 0; maximal score = 12). Seven days after TBI, brains were perfusion-fixed, coronal sections at various levels were digitized, and contusion areas in the superficial, middle and deep layers of cortex and in the underlying fimbria were measured. HSA significantly improved the neurological score compared to saline at 24 h, 72 h, and 7 days after TBI (6.0 +/- 0.6 [albumin] versus 8.4 +/- 0.5 [saline]; 3.6 +/- 0.7 versus 6.8 +/- 1.0; and 2.6 +/- 0.6 versus 5.7 +/- 0.8, respectively; p < 0.05). HSA therapy also significantly reduced total contusion area (0.89 +/- 0.2 versus 1.82 +/- 0.3 mm2; p = 0.02). Our findings document that high-concentration albumin therapy instituted 15 min after trauma significantly improves the neurological score and reduces histological damage. We believe that this pharmacological agent may have promising potential for the clinical treatment of brain injury.

Analysis of Variance↗

A significant increase in both basal and maximal calcineurin activity following fluid percussion injury in the rat.

Calcineurin, a neuronally enriched, calcium-stimulated phosphatase, is an important modulator of many neuronal processes, including several that are physiologically related to the pathology of traumatic brain injury. This study examined the effects of moderate, central fluid percussion injury on the activity of this important neuronal enzyme. Animals were sacrificed at several time-points postinjury and cortical, hippocampal, and cerebellar homogenates were assayed for calcineurin activity by dephosphorylation of p-nitrophenol phosphate. A significant brain injury-dependent increase was observed in both hippocampal and cortical homogenates under both basal and maximally-stimulated reaction conditions. This increase persisted 2-3 weeks post-injury. Brain injury did not alter substrate affinity, but did induce a significant increase in the apparent maximal dephosphorylation rate. Unlike the other brain regions, no change in calcineurin activity was observed in the cerebellum following brain injury. No brain region tested displayed a significant change in calcineurin enzyme levels as determined by Western blot, demonstrating that increased enzyme synthesis was not responsible for the observed increase in activity. The data support the conclusion that fluid percussion injury results in increased calcineurin activity in the rat forebrain. This increased activity has broad physiological implications, possibly resulting in altered cellular excitability or a greater likelihood of neuronal cell death.

Animals↗

Effects of estradiol on cognition and hippocampal pathology after lateral fluid percussion brain injury in female rats.

Studies involving animal models of acute central nervous system (CNS) stroke and trauma strongly indicate that sex and/or hormonal status are important determinants of outcome after brain injury. The present study was undertaken to examine the ability of estradiol to protect hippocampal neurons from lateral fluid percussion brain injury. Sprague-Dawley female rats (211-285 g; n = 119) were ovariectomized, and a subset (n = 66) were implanted with 17beta-estradiol pellets to provide near physiological levels of estradiol. Animals were subjected to lateral fluid percussion brain injury or sham injury 1 week later. Activation of caspase-3 (n = 26) and TUNEL staining (n = 21) were assessed at 3 and 12 h after injury, respectively, in surviving control and estradiol-treated animals. Memory retention was examined using a Morris water maze test in a separate subset of animals (n = 43) at 8 days after injury. Activated caspase-3 and TUNEL staining were observed in the dentate hilus, granule cell layer, and CA3 regions in all injured rats, indicative of selective hippocampal cell apoptosis in the acute posttraumatic period. Estradiol did not significantly alter the number of hippocampal neurons exhibiting caspase-3 activity or TUNEL staining. Brain injury impaired cognitive ability, assessed at 1 week post-injury (p < 0.001). However, estradiol at physiological levels did not significantly alter injury-induced loss of memory. These data indicate that estradiol at physiological levels does not ameliorate trauma-induced hippocampal injury or cognitive deficits in ovariectomized female rats.

Animals↗

Prophylactic use of high-frequency percussive ventilation in patients with inhalation injury.

Death and the incidence of pneumonia are significantly increased in burn patients with inhalation injury, despite application of conventional ventilatory support techniques. The effect of high-frequency percussive ventilation on mortality rate, incidence of pulmonary infection, and barotrauma were studied in 54 burn patients with documented inhalation injury admitted between March 1987 and September 1990 as compared to an historic cohort treated between 1980 and 1984. All patients satisfied clinical criteria for mechanical ventilation. High-frequency percussive ventilation was initiated within 24 hours of intubation. The patients' mean age and burn size were 32.2 years and 47.8%, respectively (ranges, 15 to 88 years; 0% to 90%). The mean number of ventilator days was 15.3 +/- 16.7 (range, 1 to 150 days), with 26% of patients ventilated for more than 2 weeks. Fourteen patients (25.9%) developed pneumonia compared to an historic frequency of 45.8% (p less than 0.005). Mortality rate was 18.5% (10 patients) with an expected historic number of deaths of 23 (95% confidence limits of 17 to 28 deaths). The documented improvement in survival rate and decrease in the incidence of pneumonia in patients treated with prophylactic high-frequency ventilation (HFV), as compared to a cohort of patients treated in the 7 years before the trial, indicates the importance of small airway patency in the pathogenesis of inhalation injury sequelae and supports further use and evaluation of HFV.

Adolescent↗