Biomedical subjects

Jean F Soustiel

Publications and source records attributed to Jean F Soustiel.

14 recordsLinked to original sources

PubMed2006

Immunohistochemical expression of peripheral benzodiazepine receptors in human astrocytomas and its correlation with grade of malignancy, proliferation, apoptosis and survival.

Peripheral benzodiazepine receptors (PBR) are widely distributed in peripheral tissues, astrocytes, and microglia of the brain. They are involved in apoptosis, proliferation, and many other processes, such as steroidogenesis in adrenal glands, male and female gonads, biological adaptation to stress, etc. It has been established that the expression of PBR in astrocytomas is higher than in the normal brain. The goal of this study was to explore the correlation of the immunohistochemical expression of PBR in astrocytomas with the grade of malignancy and rates of apoptosis, proliferation and survival. In 130 cases of astrocytomas (25 grade I, 25 grade II, 20 grade III, 60 grade IV), paraffin sections were stained immunohistochemically for PBR and MIB-1(Ki-67). TUNEL assay was used for evaluation of apoptosis. It was found that the intensity and extent of staining for PBR had a strong direct correlation with the grade of malignancy of the tumor, along with proliferative and apoptotic indices. The highest expression of PBR was in glioblastomas grade IV, especially around areas of necrosis. There was a strong negative correlation between PBR expression and survival. The results of this study may be applied in the pathological diagnosis of astrocytomas as an additional clue in establishing tumor grade; they may be used in the imaging of astrocytomas, both for diagnosis and follow-up, by the application of positron emission tomography scanning with PBR specific ligands. Targeting of PBR in high-grade gliomas may be a promising approach, achieving more specific anti-tumor effect.

Analysis of Variance↗

PubMed2006

Relative effects of mannitol and hypertonic saline on calpain activity, apoptosis and polymorphonuclear infiltration in traumatic focal brain injury.

The purpose of this study was to compare the relative effects of mannitol and hypertonic saline (HTS) on calpain activity, apoptosis and neuroinflammatory response induced by experimental cortical contusion. Four groups of 5 Sprague-Dawley male rats were submitted to focal brain injury produced by exposing the parietal cortex to dynamic cortical deformation. Groups were defined by rescucitation fluids administered 30 min post-injury as follows: group 1-0.9% normal saline 2 ml/kg; group 2-mannitol 20% 0.5 g/kg; group 3-HTS 2 ml/kg; group 4-HTS 4 ml/kg. At 72 h, animals were sacrificed. Paraffin-mounted sections of were stained for mu-Calpain, TUNEL, active caspase 3 and myeloperoxidase. There was no difference in the lesion size between the different groups. In contrast, there was a significant reduction in calpain and apoptosis activity and in the neuroinflammatory response in animals receiving HTS. Although mannitol proved to significantly decrease the neuroinflammatory response and calpain activity, it did not affect apoptosis, and its effect was significantly less than that of HTS. Importantly, the effect of HTS was mostly independent from the infused volume. Our results show that HTS promotes cell survival and reduces secondary brain damage following TBI. This protective effect was evidenced at rather small infused volumes, proved to encompass several cellular and molecular mechanisms involved in secondary cell death and could not be related to relief of intracranial pressure. These findings suggest that the high osmolality of HTS may have protective effects besides its impact on brain edema.

Animals↗

PubMed2006

Cerebral perfusion computerized tomography: influence of reference vessels, regions of interest and interobserver variability.

INTRODUCTION: There are still no standardized guidelines for perfusion computerized tomography (PCT) analysis. METHODS: A total of 61 PCT studies were analyzed using either the anterior cerebral artery (ACA) or the middle cerebral artery (MCA) as the arterial reference, and the superior sagittal sinus (SSS) or the vein of Galen (VG) as the venous reference. The sizes of regions of interest (ROI) were investigated comparing PCT results obtained using a hemispheric ROI combined with vascular pixel elimination with those obtained using five smaller ROIs located over the cortex and basal ganglia. In addition, interobserver variations were explored using a standardized protocol. RESULTS: MCA-based measurements of cerebral blood flow (CBF) and blood volume (CBV) were in accordance with those obtained with the ACA except in 16 patients with ischemic stroke, in whom CBF was overestimated by the ipsilateral MCA. Venous maximal intensity was significantly lower with the VG when compared with the SSS, resulting in overestimation of CBF and CBV. However, in 13.3% of patients the VG ROI yielded higher maximal intensities than the SSS ROI. There was no difference in PCT results between hemispheric ROI and averaged separate ROI when vascular pixel elimination was used. Finally, interobserver variations were as high as 11% for CBF and 12% for CBV. CONCLUSION: The present results suggest that pathological rather than anatomical considerations should dictate the choice of the arterial ROI. For venous ROI, although SSS seems to be adequate in most instances, deep cerebral veins may occasionally generate higher maximal intensities and should therefore be selected. Importantly, significant user-dependency should be taken into account.

Adolescent↗

PubMed2006

Gliosarcoma with liposarcomatous differentiation: the new member of the lipid-containing brain tumors family.

Gliosarcoma is a rare malignant, biphasic brain tumor composed of glioblastoma multiforme and sarcomatous components. Various types of sarcomatous differentiation are described in this tumor: fibrosarcomatous, malignant fibrous histiocytoma-like, chondrosarcomatous and osteosarcomatous types. We report an extremely unusual variant of liposarcomatous differentiation in gliosarcoma in 72-year-old woman. Fat cells were presented by atypical multivacuolar and monovacuolar lipoblasts, stained positive for S100. p53 that was positive in both glial and mesenchymal cells of the tumor were negative in the lipoblasts. To the best of our knowledge, this is the first report in the literature of liposarcomatous differentiation in gliosarcoma.

Aged↗

PubMed2005

Evaluation of the apoptosis-related proteins of the BCL-2 family in the traumatic penumbra area of the rat model of cerebral contusion, treated by hyperbaric oxygen therapy: a quantitative immunohistochemical study.

The growth and progression of traumatic brain injury (TBI) lesions depend significantly on developments in the traumatic penumbra area, perilesional region, where delayed neuronal death occurs. Recent data supports the important role of apoptosis in delayed cell death in TBI. Previously we demonstrated a significant reduction of apoptosis in traumatic penumbra in animals treated by hyperbaric oxygen (HBO). In this study we evaluate the expression of apoptosis-related proteins of the Bcl-2 family (Bcl-2, Bax and Bcl-xL) in the traumatic penumbra area in correlation with the extent of apoptosis in the rat model of focal cerebral contusion, treated by HBO. Sprague-Dawley rats underwent cortical dynamic deformation, some with subsequent hypoxemia. A group of both hypoxemic and non-hypoxemic animals was treated by HBO. The pathological study was based on immunohistochemical staining of the brain sections for Bcl-2, Bax and Bcl-xL with quantitative evaluation of staining by image analysis. The expression of Bcl-2 in hypoxemic animals was lower than in non-hypoxemic animals, but a significant increase in Bcl-2 expression was seen in both groups after HBO treatment. Bcl-xL also demonstrated an increase after HBO treatment but less significant. Staining for Bax protein did not demonstrate significant change after treatment. These data correlate well with the reduction of TUNEL-positive cells in traumatic penumbra after HBO treatment. We concluded that the apoptotic mechanisms are important in delayed cell death in TBI and that post-traumatic hypoxemia increases the intensity of apoptosis, probably through a decrease in Bcl-2 and Bcl-xL expression which normally repress apoptosis. The beneficial effect of HBO treatment in our model of brain contusion correlates well with the increased expression of anti-apoptotic proteins (Bcl-2 and Bcl-xL) following treatment and the appropriate decrease in the extent of apoptosis. In light of these results, the usage of HBO is justified as neuroprotective treatment in TBI.

Animals↗

PubMed2005

Neuroprotective anti-apoptosis effect of estrogens in traumatic brain injury.

Traumatic brain injury (TBI) is a leading cause of death and functional disability in western countries, affecting mostly young patients. Despite intense and sustained efforts deployed for the development of new therapeutic strategies, no clinical benefit has been shown by any of the investigated compounds. Increasing attention has been drawn during the past two decades to the neuroprotective effects of estrogens, although most of the available data relate to ischemic brain injury. The purpose of the present study was to investigate the potential neuroprotective value of estrogens in TBI as a therapeutic modality. For this purpose, a contusion was created in the parietal cortex by dynamic cortical deformation in two groups of 10 Sprague-Dawley male rats. Following the injury, treated animals received conjugated estrogens for 3 days, using a subcutaneously implanted osmotic pump. Animals were then sacrificed, and TUNEL, anti-active Caspase 3, bcl-2, and bax labeling were performed in paraffin-embedded brain sections, allowing for comparative and quantitative analysis. In estrogen-treated animals, there was a marked and significant reduction of apoptosis in comparison with non-treated animals. The reduction in TUNEL and active Caspase 3 staining was similar and close to 50%. Optical analysis of histological slides prepared by bcl-2 labeling showed a significant increase in bcl-2 expression in estrogen-treated animals compared to non-treated animals. On the contrary, bax expression was not influenced by hormonal treatment, and no difference could be noticed between the two groups. These results support the potential therapeutic value of estrogens in TBI and further clarify their mode of action.

Animals↗

PubMed2005

Monitoring of cerebral blood flow and metabolism in traumatic brain injury.

The aim of the present study was to investigate the course of cerebral blood flow (CBF) and metabolism in traumatic brain injury (TBI) patients and to specifically characterize the changes in lactate and glucose indices in the acute post-traumatic period with regard to neurological condition and functional outcome. For this purpose, 55 consecutive TBI patients (mean age 37 +/- 17 years, mean GCS 6.8 +/- 3.2) were prospectively and daily evaluated. Global CBF, cerebral metabolic rates of oxygen (CMRO2), glucose (CMRGlc), and lactate (CMRLct) were calculated using arterial jugular differences. In all patients, CBF was moderately decreased during the first 24 h in comparison with normal subjects although this relative oligemia was more pronounced in patients with poor outcome (p = 0.0007). Both CMRO2 and CMRGlc were significantly depressed and correlated to outcome (p < 0.0001, p = 0.0088). CMRLct analysis revealed positive values (lactate uptake) during the first 48 h, especially in patients with favorable outcome. Both CMRO2 and CMRLct correlated with GCS (p = 0.0001, p = 0.0205). CMRLct levels showed an opposite correlation with CBF in patients with favorable and poor outcome. In the former group, correlation analysis exhibited a negative slope with evidence for increasing lactate uptake associated with lower CBF values (r = -0.1940, p = 0.0242). On the contrary, in patients with adverse outcome, CMRLct values demonstrated a weak though opposite correlation with CBF (r = 0.0942, p = 0.2733). The present data emphasize the clinical significance of monitoring of cerebral blood flow and metabolism in TBI and provide evidence for metabolic coupling between astrocytes and neurons.

Adult↗

PubMed2004

The value of motor and somatosensory evoked potentials in evaluation of cervical myelopathy in the presence of peripheral neuropathy.

STUDY DESIGN: Patterns and rates of motor-evoked potential (MEP) and somatosensory-evoked potential (SEP) abnormalities were evaluated in 9 patients with combined cervical cord compression and diabetic neuropathy and 15 patients with asymptomatic cervical cord compression. The results were compared with those of 8 patients with pure cervical myelopathy and 7 patients with pure diabetic neuropathy. OBJECTIVE: To assess the efficacy of MEPs and SEPs in the evaluation of cervical myelopathy in the presence of peripheral neuropathy. SUMMARY OF BACKGROUND DATA: Previous studies have demonstrated a high sensitivity of MEPs and SEPs in documenting a functional involvement of motor and somatosensory pathways in pure or preclinical cervical myelopathy. However, there have been no detailed reports on MEPs and SEPs in cervical cord compression associated with peripheral neuropathy. METHODS: Central somatosensory conduction was assessed by median and tibial SEPs using peak-to-peak and onset-to-onset methods. Central motor conduction was measured by MEPs and F-waves elicited from upper and lower limb muscles in response to transcranial magnetic stimulation, magnetic stimulation of cervical motor roots, and electrical stimulation of peripheral nerves. RESULTS: MEPs were more sensitive than SEPs in detecting central conduction impairments in patients with either pure or preclinical or combined forms of cervical myelopathy. The rate of MEP abnormalities suggesting the corticospinal tract involvement in the combined cervical cord compression-neuropathy group did not differ significantly from that in the asymptomatic cervical cord compression group but was lower than in the pure cervical myelopathy group. Combined MEP and SEP analysis improved the test sensitivity in detecting clinically "silent" cervical cord dysfunctions. CONCLUSIONS: MEPs associated with SEPs are a valuable tool for assessing the presence and severity of cervical cord involvement in combined cervical cord compression and peripheral neuropathy lesions.

Adult↗

PubMed2004

Posttraumatic basilar artery vasospasm.

BACKGROUND: During the past decade, vasospasm following posttraumatic subarachnoid hemorrhage (tSAH) has drawn increasing attention. However, despite accumulating evidence linking this phenomenon with poorer outcome, the clinical significance of posttraumatic vasospasm is still debated and often disputed, so that no definite therapeutic attitude has yet been adopted. Recent attention has been drawn to basilar vasospasm, suggesting a negative influence on neurologic outcome. The aim of the present study was the evaluation of basilar vasospasm as an independent factor of secondary brain damage following posttraumatic hemorrhage. METHODS: Daily transcranial Doppler (TCD) evaluations were conducted in 93 consecutive patients with tSAH. Basilar artery (BA) vasospasm was defined by blood flow velocity (FV) higher than 85 cm/s for at least 2 consecutive days. RESULTS: Thirty-two patients (34.4%) had BA FVs higher than 85 cm/s. In those patients, the ratio between BA FV and mean vertebral artery FV was higher than 2.5 and below 2 and those without TCD signs of vasospasm. Using multivariate logistic regression analysis, BA vasospasm proved to independently influence neurologic outcome. CONCLUSIONS: BA vasospasm severe enough to compromise cerebral blood flow to the brainstem, although uncommon, may nevertheless have a potential deleterious effect on neural tissue sensitized by trauma. The present results suggest that specific imaging procedures and eventually therapeutic measures should be conducted in the presence of significant BA vasospasm.

Adolescent↗

PubMed2004

Hyperbaric oxygen therapy for reduction of secondary brain damage in head injury: an animal model of brain contusion.

Cerebral contusions are one the most frequent traumatic lesions and the most common indication for secondary surgical decompression. The purpose of this study was to investigate the physiology of perilesional secondary brain damage and evaluate the value of hyperbaric oxygen therapy (HBOT) in the treatment of these lesions. Five groups of five Sprague-Dawley rats each were submitted to dynamic cortical deformation (DCD) induced by negative pressure applied to the cortex. Cerebral lesions produced by DCD at the vacuum site proved to be reproducible. The study protocol entailed the following: (1) DCD alone, (2) DCD and HBOT, (3) DCD and post-operative hypoxia and HBOT, (4) DCD, post-operative hypoxia and HBOT, and (5) DCD and normobaric hyperoxia. Animals were sacrificed after 4 days. Histological sections showed localized gross tissue loss in the cortex at injury site, along with hemorrhage. In all cases, the severity of secondary brain damage was assessed by counting the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and caspase 3-positive cells in successive perilesional layers, each 0.5 mm thick. Perilesional TUNEL positive cells suggested the involvement of apoptosis in group 1 (12.24% of positive cells in layer 1). These findings were significantly enhanced by post-operative hypoxia (31.75%, p < 0.001). HBOT significantly reduced the severity and extent of secondary brain damage expressed by the number of TUNEL positive cells in each layer and the volume of the lesion (4.7% and 9% of TUNEL positive cells in layer 1 in groups 2 and 4 respectively, p < 0.0001 and p < 0.003). Normobaric hyperoxia also proved to be beneficial although in a lesser extent. This study demonstrates that the vacuum model of brain injury is a reproducible model of cerebral contusion. The current findings also suggest that HBOT may limit the growth of cerebral contusions and justify further experimental studies.

Animals↗

PubMed2004

Role of multisection CT angiography in the evaluation of vertebrobasilar vasospasm in patients with subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Optimal means for assessing cerebral vasospasm, mainly at the vertebrobasilar system, have not been established. The purpose of this study was to evaluate the role of multisection CT angiography (MCTA) in the detection and quantification of vertebrobasilar vasospasm (VBS) indicated on transcranial Doppler (TCD) imaging in patients with subarachnoid hemorrhage (SAH). METHODS: Forty-three MCTA studies of the vertebrobasilar arteries were performed with a multisection spiral CT scanner in 36 patients with SAH. Parameters used were 1-mm collimation, 0.625Q pitch, 120 kV, and 250 mAs. Contrast material was injected (80-100 mL, 3 mL/s) after a 15-20-second delay. Postprocessing of the vertebrobasilar system was performed by using maximum intensity projection and volume-rendering reconstruction. Vessel diameter was measured at different intracranial locations along the vertebral and basilar arteries perpendicular to their long axis by using curved reformatted multiplanar reformation. TCD imaging of the posterior circulation was performed within 24 hours. RESULTS: MCTA demonstrated narrowed arteries compatible with VBS in 13 patients, consistent with TCD findings. Despite TCD recordings of high flow velocity in three other patients, MCTA did not reveal vasospasm but did show wide arteries feeding arteriovenous malformations in two and normal-sized arteries in one. VBS in two patients was identified on MCTA but overlooked during TCD imaging. Twenty patients had normal findings on both TCD and MCTA studies. CONCLUSION: Cerebral MCTA is recommended as a reliable, rapid, and minimally invasive diagnostic method, one complementary to TCD imaging for assessing VBS in patients with SAH.

Adolescent↗

PubMed2003

The effect of isosorbide dinitrate, a donor of nitric oxide, on maternal cerebral blood flow in gestational hypertension and preeclampsia.

OBJECTIVE: The purpose of this study was to investigate the effect of a nitric oxide donor on cerebral perfusion pressure and other blood flow index values in the maternal middle cerebral and basilar arteries. STUDY DESIGN: Sublingual tablets of 5-mg isosorbide dinitrate were administered to 19 hypertensive pregnant patients. Doppler velocimetry of the middle cerebral and basilar arteries was obtained with a transcranial Doppler with the use of the transtemporal and suboccipital approach. RESULTS: The mean (+/-SEM) flow velocity in the middle cerebral artery significantly decreased from a baseline of 65.9 +/- 3.1 cm/s to 55.2 +/- 2.2 and 52.0 +/- 2.1 cm/s at 10 and 20 minutes (P <.0001). Resistance area product insignificantly increased from a baseline of 2.0 +/- 0.1 before isosorbide dinitrate to 2.19 +/- 0.11 at 20 minutes. No significant changes were observed in the resistance and pulsatility indices in the middle cerebral artery. The cerebral perfusion pressure did not change significantly after isosorbide dinitrate (84.5 +/- 7.3, 80.8 +/- 6.6, and 78.5 +/- 5.0 mm Hg at 0, 10, and 20 minutes, respectively) nor did the cerebral blood flow index. CONCLUSION: The results obtained demonstrate that cerebral perfusion pressure is unaltered by isosorbide dinitrate, despite significant changes in maternal blood pressure and in blood flow velocities in the middle cerebral artery.

Administration, Sublingual↗

PubMed2002

Basilar vasospasm diagnosis: investigation of a modified "Lindegaard Index" based on imaging studies and blood velocity measurements of the basilar artery.

BACKGROUND AND PURPOSE: Numerous studies have shown that cerebral vasospasm is one of the leading causes of death and neurological disability after subarachnoid hemorrhage. Most of these studies, however, have focused on anterior circulation vessels. Since the introduction of the transcranial Doppler (TCD), increasing attention has been given to basilar artery (BA) vasospasm, especially in traumatic subarachnoid hemorrhage. As shown for the anterior circulation, however, the significance of elevated flow velocities (FVs) in the posterior vessels may be ambiguous, so vasospasm may not be reliably differentiated from hyperemia. The purpose of the present study was to evaluate the potential additional value of an intracranial/extracranial FV ratio in the posterior circulation to cope with this shortcoming of the TCD in the diagnosis of BA vasospasm. METHODS: FV in the extracranial vertebral artery (VA) was measured in 20 healthy volunteers. Normative values of an intracranial/extracranial VA FV ratio (IVA/EVA) and a BA/extracranial VA FV ratio (BA/EVA) were calculated. Thirty-four patients with subarachnoid hemorrhage were then evaluated with TCD and CT angiography (CTA). The value of the IVA/EVA and BA/EVA ratios in the diagnosis and assessment of vertebrobasilar vasospasm was investigated. RESULTS: The extracranial VA could be insonated in all subjects at depths ranging from 45 to 55 mm. The average FV for the extracranial VA was 26 cm/s. The ratios between intracranial and extracranial VA FVs were 1.6 on both sides, whereas the ratio between the BA FVs and the mean extracranial VA FVs was slightly higher at 1.7. Fourteen patients (41.2%) had CTA evidence of BA vasospasm. Vasospasm was severe in 7 patients, moderate in 1, and mild in the remaining. An FV threshold of 80 cm/s was indicative of BA vasospasm in 92.8% with 3 false-positive results that could be related to vertebrobasilar hyperemia. Comparative analysis between CTA and TCD findings showed that BA/EVA was >2 in all patients with BA vasospasm (100% sensitivity) and < 2 in all but 1 patient without BA vasospasm (95% specificity). Furthermore, the BA/EVA ratio showed a close correlation with BA diameter (r=-0.8139, P<0.0001) and was >3 in all patients with severe vasospasm. CONCLUSIONS: The results of the present study showed that the BA/EVA ratio may contribute to an improved discrimination between BA vasospasm and vertebrobasilar hyperemia and enhance the accuracy and reliability of TCD in the diagnosis of BA vasospasm. Our data further suggest that the BA/EVA ratio may provide an approximation of vasospasm severity and help in identifying patients who are likely to suffer from hemodynamically significant vasospasm.

Adolescent↗

PubMed2002

A new angle-independent Doppler ultrasonic device for assessment of blood flow volume in the extracranial internal carotid artery.

OBJECTIVE: To evaluate a new angle-independent ultrasonic device for assessment of blood flow volume in the internal carotid artery. METHODS: In vitro, a pulsatile pump was set to provide an outflow of physiological fluid at 500 mL/min through an 8-mm-diameter tube. Flow volume rates were measured 10 times by 10 different operators and compared with time-collected flow volume rates. In vivo, internal and common carotid artery blood flow volumes were measured in 28 volunteers by 2 operators using a FlowGuard device (Biosonix Ltd). Internal and common carotid artery diameters and blood flow volumes were also assessed by Duplex sonography and compared with FlowGuard measurements. In 10 volunteers, internal carotid artery blood flow volume changes in response to monitored breath manipulations were recorded. RESULTS: In vitro, intraoperator variability was 4.04% (range, 2%-5.7%). The mean error rate +/- SD was 3.54% +/- 0.8% (range, 2.7%-5.2%). In vivo, the mean common carotid artery blood flow volume was 456 +/- 39 mL/min (range, 417-583 mL/min) with a mean diameter of 6.7 +/- 0.7 mm (range, 5.8-8.7 mm). The mean internal carotid artery blood flow volume was 277 +/- 25 mL/min (range, 239-338 mL/min) with a mean diameter of 5 +/- 0.5 mm (range, 4.1-6.1 mm). No significant difference was found between operators. Internal carotid artery diameter and blood flow volume measured by the FlowGuard were closely correlated with the results of Duplex sonography. Repeated shifts of end-tidal CO2 induced reproducible changes in internal carotid artery flow volume: 187.5 +/- 18.1 mL/min at 26.8 +/- 1.9 mm Hg and 382.1 +/- 18.2 mL/min at 47 +/- 2.2 mm Hg. CONCLUSIONS: The FlowGuard showed that volume flow studies in the internal carotid artery could be easily performed, with results compatible with those of previous clinical reports. Duplex comparative results and breath-induced changes in internal carotid artery flow volume justify further evaluation of the system.

Adult↗