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Biomedical subjects

A Marmarou

Publications and source records attributed to A Marmarou.

At least 37 records · Page 2Linked to original sources
PubMed2002

Diffuse brain injury complicated by acute subdural hematoma and secondary insults in the rodents: the effect of surgical evacuation.

Head Trauma associated with acute sudural hematoma (SDH) and complicated by secondary insult is a grave clinical combination with complex pathophysiology. The aim of this study was to develop a clinically relevant injury model, which can be used to study the interaction between injury mechanisms. We present a novel model of SDH combined with diffuse brain injury (DBI) and a hypoxic secondary insult, and investigate the effects of surgical evacuation. Adult Sprague-Dawley rats were given a 300 microliters SDH and 20 minute-hypoxia following Impact Acceleration DBI. Hematoma was evacuated at one hour post-injury. Physiological parameters were measured for 5 hours, together with assessment of brain water content. Secondary insult after traumatic SDH was associated with significant brain swelling and stimulated refractory rise in ICP. In traumatic SDH complicated by secondary insult, brain swelling is exacerbated by surgical evacuation.

Animals↗
PubMed2002

Diffuse brain injury complicated by acute subdural hematoma in the rodents: the effect of early or delayed surgical evacuation.

Of all the possible clinical factors affecting the outcome of patients suffering acute subdural hematomas (SDH), timing of surgical evacuation is certainly the most debated. The purpose of this study was to develop an experimental model able to reproduce the clinical behavior of post-traumatic SDH as observed in head injured patients. We present a novel model of SDH combined with diffuse brain injury (DBI), and investigate the effects of early and delayed surgical evacuation. Following Impact Acceleration DBI, adult Sprague-Dawley rats were given a 400 microliters SDH. Hematoma was then evacuated at one (rapid evacuation) or four hours (delayed evacuation) post-injury. Physiological parameters were measured for 5 hours, followed by the assessment of brain water content. In this experimental model, there is strong evidence that trauma acts synergistically with SDH enhancing brain edema formation and increasing ICP. In absence of secondary insult, rapid evacuation of traumatic SDH limits exposure to high ICP, reduces brain edema and is beneficial.

Animals↗
PubMed2002

Application of chemical shift imaging for measurement of NAA in head injured patients.

Neurochemical damage following brain injury can be assessed non-invasively by measurement of N-Acetyl-Aspartate (NAA) using Proton Magnetic Resonance Spectroscopy (1HMRS). This report documents results of applying Chemical Shift Imaging (CSI) postprocessing for measuring NAA in traumatically injured brain. Following stabilization, severely head-injured patients (GCS 8 or less) were transported to the MRI suite. Semi-quantitative measurement of NAA, creatine (Cr/PCr) and choline (Cho) were obtained from single voxels (8 cm3) and CSI for acquisition of smaller voxels (2 cm3) throughout areas of the brain. Studies were completed with no complication. In focal injury, SVS positioned at the site of lesion demonstrated reduced NAA, compared to contralateral hemisphere. In diffuse injury, CSI demonstrated uniform reduction of NAA throughout the brain. NAA/Cho showed normal levels within 24 hours of injury averaging 2.4 and decreased over the next 10 days reaching a plateau of 0.75. At 30 days, NAA showed no recovery in poor outcome patients. In patients with good outcome, NAA initially low recovered near baseline levels. CSI provides a comprehensive neurochemical assessment of neuronal damage. NAA decreases and remains low in patients with poor outcome. NAA recovers in patients with favorable outcome, suggesting marginal metabolic impairment and possible re-synthesis of the NAA pool.

Aspartic Acid↗
PubMed2001

Continuous negative abdominal pressure device to treat pseudotumor cerebri.

OBJECTIVE: To study the effects of an externally applied negative abdominal pressure device designed to lower the effects of intra-abdominal pressure (IAP) on headaches and pulsatile tinnitus in severely obese women with pseudotumor cerebri (PTC). DESIGN: Short-term clinical intervention trial in the Clinical Research Center. Days 1 and 3 were 'control' days; on days 2 and 4-6 patients were in the device from 8:00 am to noon and from 1:00 to 5:00 pm, and on nights 7-11 they were in the device from 10:00 pm to 8:00 am. The last four patients were treated in a device with a counter-traction mechanism. SUBJECTS: Seven centrally obese women with PTC. MEASUREMENTS: Headache and pulsatile tinnitus severity were graded by the patient using visual analog scale (1-10) and averaged for the time that the device was in use or not in use. IAP was estimated from urinary bladder pressure (UBP) before and during device use. The internal jugular vein (IJV) elliptical cross-sectional area was measured with B-mode ultrasonography; the timed average velocity was measured by Doppler. RESULTS: There was a decrease in both headache (6.8+/-0.8 to 4.2+/-0.8, P<0.05) and pulsatile tinnitus (4.2+/-0.5 to 1.8+/-0.5, P<0.02) within 5 min, and in headache (to 2.2+/-0.8, P<0.01) and tinnitus (to 1.7+/-0.5, P<0.01) within 1 h of device activation. UBP decreased (P<0.001) from 19.1+/-3 to 12.5+/-2.8 cmH2O. Headache remained improved throughout time that the device was used. During the second week, five of seven patients slept in the device without difficulty and four awoke without headache. There was a progressive decrease (P<0.01) in headache during the day after sleeping in the device at night as compared with days 1 and 3 when it was not used (6.5+/-0.5, day 1; 4.1+/-0.7, day 3; 3.1+/-0.8, day 8; 2.3+/-0.8, day 10). Headaches returned late in the afternoon in two patients; the device was reactivated and headache again improved. Five patients underwent IJV sonography; the IJV area decreased (129+/-53 to 100+/-44 mm2, P=0.06) without a change in IJV flow (1004+/-802 to 1000+/-589 ml/min) with the device. When activated, the device was pulled into the patient, creating discomfort that was alleviated with the counter-traction mechanism in the last four patients. One patient developed a 5 cm area of blisters that resolved when the device was worn over a hospital gown. CONCLUSIONS: Decreasing IAP relieved headaches and pulsatile tinnitus in PTC. When patients slept in the device, they awoke without headache or tinnitus, which remained markedly improved throughout most of the following day. This study supports the hypothesis that PTC in obese women is secondary to an increased IAP.

Abdomen↗
PubMed2001

N-Acetylaspartate reduction as a measure of injury severity and mitochondrial dysfunction following diffuse traumatic brain injury.

N-Acetylaspartate (NAA) is considered a neuron-specific metabolite and its reduction a marker of neuronal loss. The objective of this study was to evaluate the time course of NAA changes in varying grades of traumatic brain injury (TBI), in concert with the disturbance of energy metabolites (ATP). Since NAA is synthesized by the mitochondria, it was hypothesized that changes in NAA would follow ATP. The impact acceleration model was used to produce three grades of TBI. Sprague-Dawley rats were divided into the following four groups: sham control (n = 12); moderate TBI (n = 36); severe TBI (n = 36); and severe TBI coupled with hypoxia-hypotension (n = 16). Animals were sacrificed at different time points ranging from 1 min to 120 h postinjury, and the brain was processed for high-performance liquid chromatography (HPLC) analysis of NAA and ATP. After moderate TBI, NAA reduced gradually by 35% at 6 h and 46% at 15 h, accompanied by a 57% and 45% reduction in ATP. A spontaneous recovery of NAA to 86% of baseline at 120 h was paralleled by a restoration in ATP. In severe TBI, NAA fell suddenly and did not recover, showing critical reduction (60%) at 48 h. ATP was reduced by 70% and also did not recover. Maximum NAA and ATP decrease occurred with secondary insult (80% and 90%, respectively, at 48 h). These data show that, at 48 h post diffuse TBI, reduction of NAA is graded according to the severity of insult. NAA recovers if the degree of injury is moderate and not accompanied by secondary insult. The highly similar time course and correlation between NAA and ATP supports the notion that NAA reduction is related to energetic impairment.

Adenosine Triphosphate↗
PubMed2001

Contrasting effects of dopamine therapy in experimental brain injury.

Management of cerebral perfusion pressure (CPP) is thought to be important for the treatment of traumatic brain injury (TBI). Vasopressors have been advocated as a method of increasing mean arterial blood pressure (mABP) and cerebral perfusion pressure (CPP) in the face of rising intracranial pressure (ICP). There are unresolved issues and theoretical risks about this therapy. This study therefore examined the effects of dopamine on physiological and MRI/MRS parameters in (1) a rodent model of rapidly rising intracranial pressure, caused by diffuse injury with secondary insult and (2) a model of cortical contusion. Dopamine was capable of restoring CPP in the model of rapidly rising ICP. This CPP restoration was associated with a partial restoration of CBF. Two profiles of change in the Apparent Diffusion Coefficient of water (ADCw) were seen; one in which ADCw recovered to baseline, and one in which ADCw remained persistently low. Dopamine did not alter these profiles. MRI assessed tissue water content was increased four hours after injury and dopamine increased cerebral water content in both subgroups of injury; significantly in the group with a persistently low ADCw (p < 0.01). In contusional injury, dopamine significantly worsened edema in both the ipsi- and contralateral hippocampus and temporal cortex. This occurred in the absence of ADCw changes, except in the contralateral hippocampus, where both water content and ADCw values rose with treatment, suggesting extracellular accumulation of water. In conclusion, although dopamine is capable of partially restoring CBF after injury, situations exist in which dopamine therapy worsens the swelling process. It is possible therefore that subgroups of patients exist who experience adverse effects of vasopressor treatment, and consequently the effects of vasopressor therapy in the clinical setting need to be more carefully evaluated.

Animals↗
PubMed2000

Ion-pairing high-performance liquid chromatographic method for the detection of N-acetylaspartate and N-acetylglutamate in cerebral tissue extracts.

An ion-pairing high-performance liquid chromatographic method for the determination of N-acetylaspartate and N-acetylglutamate using a C-18 column and a UV detection at 210 nm wavelength, by means of a diode array detector, is presented. A buffer containing 2.8 mM tetrabutylammonium hydroxide, 25 mM KH(2)PO(4), 1.25% methanol, pH 7. 00, is utilized for the isocratic separation of these N-acetylated amino acids, at a flow rate of 1 ml/min and a column temperature of 23 degrees C. The suitability of this chromatographic separation (without additional chromatographic steps prior to HPLC assay) to monitor variations both of N-acetylaspartate and of N-acetylglutamate in perchloric acid brain extracts from rats subjected to the impact acceleration model of diffuse brain injury is also reported. According to the data presented, this HPLC method allows the separation of the two N-acetylated amino acids considered from the many possible interfering compounds, commonly present in extracts of cerebral tissue, which have high extinction coefficients at 210 nm wavelength. Values of N-acetylaspartate and N-acetylglutamate determined by this method showed that cerebral trauma negatively affects both compounds, according to the severity of trauma itself.

Animals↗
PubMed2000

The permissive nature of blood brain barrier (BBB) opening in edema formation following traumatic brain injury.

The contribution of blood brain barrier opening to traumatic brain edema is not known. This study compares the course of traumatic BBB disruption and edema formation, with the hypothesis that they are not obligately related. Sprague-Dawley rats were divided into three groups: Group A (n = 47)--Impact Acceleration (IAM); Group B (n = 104)--lateral cortical impact (CCI); Group C (n = 26)--IAM + hypoxia & hypotension (THH). BBB integrity was assessed using i.v. markers (Evan's Blue, or gadolinium-DTPA). Edema formation was evaluated with gravimetry, and T1-weighted MRI. In IAM, BBB opened immediately but closed rapidly, and remained closed for at least the next 36 hours whilst 24-hour hemispheric water content (HWC) rose by 0.9% (p < 0.01). In CCI, BBB opened in both hemispheres for up to 4 hours; four hour HWC in the uninjured hemisphere was indistinguishable from Sham, where HWC in the injured hemisphere rose by approximately 1.5% (p < 0.005). We distinguished two THH animals based on Apparent Diffusion Coefficient (ADC) recovery: in ADC-recovery animals 4 hour cortical water content (CWC) was 80.4 +/- 0.6%, cf 81.4 +/- 1.3% in ADC-non-recovery (p < 0.05). In all animals the BBB was open, however two populations of permeability were seen which likely related to flow-limited extravasation of gadolinium. In IAM edema forms despite only brief BBB opening. Although there is diffuse BBB opening with lateral contusion, edema only forms in the injured hemisphere. In THH, edema formation in the face of a widely permeable barrier is driven by ADC changes or cell swelling. Edema formation clearly does not correspond with BBB opening and an open BBB is clearly not required for edema formation. However we hypothesize that a permeable BBB permissively worsens the process, by acting as a low resistance pathway for ion and water movement. These findings are consistent with our general hypothesis that edema formation after TBI is mainly cytotoxic.

Animals↗
PubMed2000

The effects of dopamine on edema formation in two models of traumatic brain injury.

The risk of vasopressors worsening cerebral edema has been raised. Previously we have reported that dopamine was able to restore cerebral blood flow in a model of monotonically rising intracranial pressure. In this study the effects of dopamine on cortical contusion and diffuse injury with secondary insult are examined. Adult male rats were divided into two groups: group 1 (n = 32)--Impact Acceleration Injury (IAM) with 30 minutes hypoxia and hypotension; group 2 (n = 12)--controlled cortical impact (6.0 m/sec, 3 mm depth). Dopamine was administered 2 hours post-injury (10-60 micrograms/kg/min i.v.). Cerebral water content and apparent diffusion coefficients (ADC) values were measured at baseline and four hours post-injury using MRI. Preinjury water content was the same in each group. Group 1 was subdivided into Groups 1A & 1B based on the ADC profile. Post-injury water content in Group 1A did not differ between saline or dopamine treated animals. Water content was higher in Group 1B-dopamine (83.4 +/- 1.1%) than Group 1B-saline animals (81.4 +/- 1.3%, p = 0.006). Contusion caused significant edema formation, however there was no significant difference between the dopamine treated or untreated group when considering either ipsilateral or contralateral cortex. Dopamine however significantly worsened edema in ipsilateral and contralateral hippocampus and both temporal cortices. ADC remained unchanged except in the contralateral hippocampus where both water content and ADC rose with dopamine suggesting precipitation of a vasogenic edema. In this study dopamine clearly worsened edema formation in two models of traumatic brain injury, and we conclude that there may be analogous clinical situations; therefore pressors should not be considered a 'blanket' therapy for all patients with a low cerebral perfusion pressure.

Animals↗
PubMed2000

The synergistic effect of acute subdural hematoma combined with diffuse traumatic brain injury on brain edema.

It is well-documented that acute subdural hematoma (ASDH) following diffuse traumatic brain injury (dTBI) contributes to severe disability and high mortality. The objective of this study was to characterize edema formation in a model of ASDH and ASDH following dTBI. Eighteen Sprague-Dawley rats were separated into three groups: Sham operated (n = 6), ASDH (n = 6), ASDH following dTBI (n = 6). Diffuse TBI was produced via the Impact-Acceleration Model [10]. ASDH was induced in the left hemisphere using the well-described method [11]. Total tissue water content was determined 4 hours after TBI utilizing wet-weight/dry-weight assessment. Our results show that ASDH causes a significant increase in tissue water content in the left hemisphere (79.2 +/- 0.7%) compared with the contralateral hemisphere (78.5 +/- 0.5%, p = 0.009). Animals exposed to ASDH following dTBI had significantly greater edema formation than those with ASDH (right: 80.9 +/- 0.4%, left: 80.5 +/- 0.7, p = 0.008). There was no significant difference between the left and right hemisphere. We conclude that edema formation in ASDH is worsened by the combination of dTBI and ASDH. Furthermore a diffuse and focal injury in combination retain the features of the diffuse injury, but with increased severity. Further studies are required to elucidate the synergistic mechanisms involved in these pathological processes.

Animals↗
PubMed2000

Characterizing edema associated with cortical contusion and secondary insult using magnetic resonance spectroscopy.

It is traditionally believed that edema associated with brain contusion is vasogenic. The objective of this study was to quantify and characterize the edema in cortical contusion coupled with early hypoxia and hypotension. Sprague-Dawley rats were randomised into six groups: Sham, Trauma moderate (Tm), Trauma severe (Ts), Hypoxia and Hypotension (HH), Tm and Ts with HH (THHm; THHs). Trauma was induced with controlled cortical impact; associated secondary insults lasted 30 minutes. Water content was measured using tissue longitudinal relaxation time (T1). Apparent diffusion coefficient of water (ADC) was calculated from diffusion-weighted imaging and single voxel spectroscopy. In the trauma groups ICP increased at 30 minutes post trauma (p < 0.05) and then gradually decreased. Only in the THH groups, ICP showed a trend to continually rise. No ICP variations were seen in the others groups. The increase in water content at 4 hours post trauma was inversely related to ADC variation (p < 0.0001). A significant increase in water content with low ADC, developed in the injured region in Ts, THHm (p < 0.05) and THHs (p < 0.01) compared to Sham. Intracellular water rose in the whole brain in THH groups although more severely in the THHs (p < 0.01). Immediately after trauma ADC fell in the THH groups, but gradually increased in the THHm, whereas there was no recovery in THHs. The results indicate that the type of edema in the injured area, with and without superimposed secondary insult, is predominantly cytotoxic (cellular). Moreover, secondary insults act synergistically with focal injury to increase cellular water in both injured tissue and remote regions.

Animals↗
PubMed2000

Comparison of NAA measures by MRS and HPLC.

This work investigates the accuracy of an in vivo estimation of absolute N-acetyl aspartate (NAA) concentrations by magnetic resonance spectroscopy (MRS) using cerebral water as an internal reference standard. Single-voxel, proton spectroscopy was carried out in two groups of rats (normal and diffuse head injury), using a PRESS sequence with TR = 3 s, TE = 135 ms. Fully relaxed water spectra and water-suppressed proton spectra were obtained from a 7 x 5 x 5 mm3 volume of tissue. MRI-based brain water content measurements were also performed. Following MRS, HPLC determinations of NAA were carried out. In the normal rats the MRS yielded 10.98 +/- 0.83 mmol/kg w.w. vs 10.76 +/- 0.76 for HPLC with a mean absolute difference of 0.8. In the injured rats the corresponding results were 9.41 +/- 1.78 (MRS) and 8.16 +/- 0.77 (HPLC) with a mean absolute difference of 1.66. The in vivo absolute method accurately documented the temporal NAA changes compared to the NAA/Cr approach.

Animals↗
PubMed2000

Distinguishing between cellular and vasogenic edema in head injured patients with focal lesions using magnetic resonance imaging.

Having determined that edema and not vascular engorgement is the major factor leading to traumatic brain swelling, the objective of this study was to determine which type of edema, cellular or vasogenic, is responsible for increased tissue water in patients with focal lesions. Severely head injured patients (GCS 8 or less) were transported to imaging suites for measurement of brain water and apparent diffusion coefficient (ADC) using magnetic resonance technique. Cerebral blood flow by stable Xenon method was also measured in the regions of interest. Brain water was increased significantly in the hemisphere with lesion. The increase in water was associated with reduced ADC signifying a predominant cellular edema. The ADC in the contralateral hemisphere was near normal value. Cerebral blood flow values in the regions of interest were above ischemic levels suggesting that factors other than ischemia are responsible for the cytotoxic swelling in patients with focal injury.

Blood-Brain Barrier↗
PubMed2000

The effects of human corticotrophin releasing factor on motor and cognitive deficits after impact acceleration injury.

Corticotrophin releasing factor has been shown in several models of tissue injury to be an effective treatment for edema. In a previous study we demonstrated this ability in two models of traumatic brain injury (TBI). The aim of this study was to assess whether human corticotrophin releasing factor (hCRF) could additionally improve motor and cognitive deficits. Adult male Sprague-Dawley rats were randomised into five groups and injured with the Impact Acceleration Model of TBI. Groups I and II received sham injury followed by treatment with either drug vehicle or 100 micrograms kg-1 hCRF respectively. Group III was injured with no treatment; Group IV animals were injured and treated with 50 micrograms kg-1 hCRF and Group V were injured and treated with 100 micrograms kg-1 hCRF. Animals were assessed both before and after injury with a battery of standardised neuropsychological tests including the Morris Water Maze, the Beam Walk Test, the Beam Balance Test and the Inclined Plane Test. Both 50 micrograms kg-1 and 100 micrograms kg-1 hCRF caused significant improvements in motor and cognitive functioning, confirming that in addition to edema-reducing properties, human corticotrophin releasing factor is also capable of improving motor and cognitive functioning. Given the beneficial experimental effects of this compound, hCRF may be a useful clinical treatment, which requires formal evaluation.

Animals↗
PubMed2000

Contribution of edema and cerebral blood volume to traumatic brain swelling in head-injured patients.

OBJECT: The pathogenesis of traumatic brain swelling remains unclear. The generally held view is that brain swelling is caused primarily by vascular engorgement and that edema plays a relatively minor role in the swelling process. The goal of this study was to examine the roles of cerebral blood volume (CBV) and edema in traumatic brain swelling. METHODS: Both brain-tissue water and CBV were measured in 76 head-injured patients, and the relative contribution of edema and blood to total brain swelling was determined. Comparable measures of brain-tissue water were obtained in 30 healthy volunteers and CBV in seven volunteers. Brain edema was measured using magnetic resonance imaging, implementing a new technique for accurate measurement of total tissue water. Measurements of CBV in a subgroup of 31 head-injured patients were based on consecutive measures of cerebral blood flow (CBF) obtained using stable xenon and calculation of mean transit time by dynamic computerized tomography scanning after a rapid bolus injection of iodinated contrast material. The mean (+/- standard deviation) percentage of swelling due to water was 9.37+/-8.7%, whereas that due to blood was -0.8+/-1.32%. CONCLUSIONS: The results of this study showed that brain edema is the major fluid component contributing to traumatic brain swelling. Moreover, CBV is reduced in proportion to CBF reduction following severe brain injury.

Adolescent↗
PubMed1999

Treatment of raised intracranial pressure following traumatic brain injury.

Appropriate treatment of raised intracranial pressure (ICP) after traumatic brain injury (TBI) remains a controversial topic in neurotraumatology. Several techniques are employed clinically, which include vasopressors, osmotically active substances, hyperventilation, and decompressive surgery. This article reviews six recent papers that have examined alternative methods of treating elevated ICP. The first two papers consider a new and controversial alternative to cerebral perfusion pressure (CPP) management, which involves mild hypotension coupled with pre-capillary vasoconstriction using dihydroergotamine. The authors claim success with this treatment, and although the patient numbers are small, there is no evidence that they fare any less well than patients treated with conventional techniques. The third and fourth papers consider hypertonic saline (HTS) as a possible osmotic treatment for raised ICP. The third examines HTS given as a 23.4% bolus and found beneficial effects. The fourth examines HTS as a 1.6% constant infusion for fluid replacement and found that patients fared less well. The reason for this difference between the results for the two administration methods is unknown, although it may relate to the triggering of body homeostatic mechanisms in the case of constant infusion. The fifth paper compares glycerol and mannitol as osmotic ICP agents and found no significant differences between them. The final study reports for the first time a series of patients treated for refractory elevations in ICP with bifrontal craniectomy. They report good results, and suggest that this therapy should be formalized as a treatment option for severely elevated ICP. The pathophysiological mechanisms underlying the generation of a raised ICP belie the use of one therapy to treat all cases. Analysis of these studies demonstrates how problematic heterogeneity in the injury population can be for the assessment of possible treatments. It is clear, therefore, that effective analysis of treatments for raised ICP requires appropriate subdivision of the injured population into common pathophysiological processes and, furthermore, that the future of clinical TBI management may well require a similar stratification in order to tailor treatments for the individual patient.

Journal Article↗
PubMed1999

CSF and ECF glutamate concentrations in head injured patients.

Excitatory Amino Acids (EAAs) release has been considered to be neurotoxic in traumatic brain injury patients. Microdialysis samples of extracellular space (ECS) and high glutamate concentrations in cerebrospinal fluid (CSF) following Traumatic Brain Injury (TBI) have been documented. The objective of this study was to determine the correlation between EAA release in ECS and CSF in focal and diffuse injury. Head injury patients (GCS < or = 8, n = 16) admitted to Medical College of Virginia Hospital were instrumented for microdialysis collection of ECS samples. CSF samples were collected through the external ventricular drainage catheter at four hour intervals for the first four days following injury. As a control group, CSF was collected from normal pressure hydrocephalus patients (n = 6). Elevated glutamate levels were observed in both CSF and ECS following head injury. The average glutamate concentration in CSF (3.20 +/- 3.62 mumol/l) was significantly increased from control levels (1.13 +/- 0.49 mumol/l, p < 0.05). Comparison of CSF and extracellular fluid (ECF) samples showed that the glutamate concentrations were maximal on the first and second days and gradually decreased on days 3 and 4. On days 4, the level of the glutamate had remained elevated above the normal level.

Adult↗