Clinical Usefulness of Transcranial Doppler as a Screening Tool for Early Cerebral Hypoxic Episodes in Patients with Moderate and Severe Traumatic Brain Injury.

BACKGROUND: Brain tissue oxygenation (PbtO2) in traumatic brain injury (TBI) is known to be dependent on cerebral blood flow (CBF) which remains difficult to assess during the very early phase of TBI management. This study evaluates if blood flow velocity measurement with 2D color-coded transcranial Doppler (TCD) can predict cerebral hypoxic episodes in moderate-to-severe TBI measured with a PbtO2 probe. METHODS: This is a prospective observational study of serial TCD measurements to assess blood flow velocity and its association with PbtO2. Measurements were done bilaterally on the middle cerebral artery (MCA) early after the insertion of PbtO2 monitoring, daily for 5 days and during dynamic challenge tests. Physiological parameters affecting PbtO2 and Doppler velocities were collected simultaneously (PaO2, PaCO2, hemoglobin [Hb] level, intracranial pressure, and cerebral perfusion pressure [CPP]). RESULTS: We enrolled 17 consecutive patients with a total of 85 TCD studies. Using 2D color-coded TCD, signal acquisition was successful in 96% of the cases. Twenty-nine (34%) TCD measures were performed during an episode of cerebral hypoxia (PbtO2 ≤ 20 mmHg). For early episodes of cerebral hypoxia (occurring ≤ 24 h from trauma), all Vmean < 40 cm/s were associated with an ipsilateral PbtO2 ≤ 20 mmHg (positive predictive value 100%). However, when considering all readings over the course of the study, however, we found no correlation between PbtO2 and MCA's mean blood flow velocity (Vmean). Vmean is also positively correlated with PaCO2, whereas PbtO2 is also correlated with PaO2, CPP, and Hb level. CONCLUSIONS: Early TCD measurements compatible with low CBF (mean velocity < 40 cm/s) detect brain tissue hypoxia early after TBI (≤ 24 h) and could potentially be used as a screening tool before invasive monitoring insertion to help minimize time-sensitive secondary injury. Various factors influence the relationship between Vmean and PbtO2, affecting interpretation of their interaction after 24 h.

Atorvastatin ameliorates early brain injury through inhibition of apoptosis and ER stress in a rat model of subarachnoid hemorrhage.

Aneurysmal subarachnoid hemorrhage (SAH) is a severe cerebrovascular disease with very poor prognosis. The aim of the present study was to evaluate the protective effects of atorvastatin on early brain injury (EBI) after SAH using a perforation SAH model. Male Sprague-Dawley rats were randomly divided into four groups: the sham group, the SAH group (model group), SAH + 10 mg.kg-1day-1 atorvastatin (low atorvastatin group), and SAH + 20 mg.kg-1day-1 atorvastatin (high atorvastatin group). Atorvastatin was administered orally by gastric gavage for 15 days before operation. At 24 h after SAH, we evaluated the effects of atorvastatin on brain water content, apoptosis by TUNEL assay and scanning electron microscope (SEM), and the expression of apoptosis-related proteins by immunofluorescence and Western blotting analysis. Compared with the sham group, we observed increased brain water content, significant apoptosis, and elevated levels of apoptosis-related proteins including caspase-3, CCAAT enhancer-binding protein homologous protein (CHOP), the 78-kDa glucose-regulated protein (GRP78), and aquaporin-4 (AQP4) in the SAH group. Atorvastatin administration under all doses could significantly reduce brain water content, apoptosis, and the expression levels of caspase-3, CHOP, GRP78, and AQP4 at 24 h after SAH. Our data show that early treatment with atorvastatin effectively ameliorates EBI after SAH through anti-apoptotic effects and the effects might be associated inhibition of caspase-3 and endoplasmic reticulum (ER) stress related proteins CHOP and GRP78.

Neuroprotective Effects of Valproic Acid on Blood-Brain Barrier Disruption and Apoptosis-Related Early Brain Injury in Rats Subjected to Subarachnoid Hemorrhage Are Modulated by Heat Shock Protein 70/Matrix Metalloproteinases and Heat Shock Protein 70/AKT Pathways.

BACKGROUND: Blood-brain barrier (BBB) disruption and neural apoptosis are thought to promote early brain injury (EBI) after subarachnoid hemorrhage (SAH). Previous studies have demonstrated that valproic acid (VPA) decreased brain injury in a prechiasmatic injection model of SAH in mice. It should be noted that the beneficial effects of VPA and the underlying mechanisms have not been fully elucidated. OBJECTIVE: To characterize the effects of VPA on BBB disruption and neural apoptosis and to determine mechanisms involved in EBI after SAH. METHODS: An endovascular perforation model was used to induce SAH in rats. VPA (300 mg/kg) was promptly administered after SAH induction, and the same dose was given 12 hours later. Quercetin (100 mg/kg), an inhibitor of heat shock protein 70 (HSP70), was injected into the peritoneum 2 hours before SAH induction. Mortality, SAH grades, neurological function, Evans Blue extravasation, brain edema, transmission electron microscopy, Western blot, double fluorescence labeling, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling staining also were used. RESULTS: VPA treatment decreased BBB disruption and brain edema, attenuated neural apoptosis, and improved neurobehavioral functions in EBI after SAH. Double fluorescence labeling indicated that matrix metallopeptidase 9 (MMP-9) was located predominately in neurons and endothelial cells. VPA upregulated the expression of HSP70, effectively decreased the expression and activity of MMP-9, and reduced claudin-5 and occludin degradation. Meanwhile, VPA also upregulated the expression of phosphorylated Akt and bcl-2. Both the anti-BBB disruption and antiapoptotic effects of VPA were abolished by quercetin. CONCLUSION: VPA prevented BBB disruption and alleviated neural apoptosis after SAH. The action of VPA appeared to be mediated though the HSP70/MMPs and HSP70/Akt pathways. ABBREVIATIONS: BBB, blood-brain barrierEBI, early brain injuryHSP, heat shock proteinMMP, matrix metalloproteinasePBS, phosphate-buffered salineSAH, subarachnoid hemorrhageTUNEL, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelingVPA, valproic acid.

Early change of plasma and cerebrospinal fluid arginine vasopressin in traumatic subarachnoid hemorrhage.

OBJECTIVE: To investigate the changes and effects of arginine vasopressin (AVP) in patients with acute traumatic subarachnoid hemorrhage (tSAH). METHODS: The plasma and cerebrospinal fluid (CSF) level of AVP, and intracranial pressure (ICP) were measured in a total of 21 patients within 24 hours after tSAH. The neurological status of the patients was evaluated by Glasgow Coma Scale (GCS). Correlation between AVP and ICP, GCS was analyzed respectively. Meanwhile, 18 healthy volunteers were recruited as control group. RESULTS: Compared with control group, the levels (pg/ml) of AVP in plasma and CSF (x+/-s) in tSAH group were significantly increased within 24 hours (38.72+/-24.71 vs 4.54+/-1.38 and 34.61+/-21.43 vs 4.13+/-.26, P less than 0.01), and was remarkably higher in GCS less than or equal to 8 group than GCS larger than 8 group (50.96+/-36.81 vs 25.26+/-12.87 and 44.68+/-31.72 vs 23.53+/-10.94, P less than 0.05). The CSF AVP level was correlated with ICP (r eqaul to 0.46, P less than 0.05), but no statistically significant correlation was found between plasma AVP, CSF AVP and initial GCS (r equal to -0.29, P larger than 0.05 and r equal to -0.32, P larger than 0.05, respectively). The ICP (mm Hg) in tSAH patients was elevated and higher in GCS less than or equal to 8 group than in GCS larger than 8 group (25.9+/-9.7 vs 17.6+/-5.2, P less than 0.05). CONCLUSION: Our research suggests that AVP is correlated with the severity of tSAH, and may be involved in the pathophysiological process of brain damage in the early stage after tSAH. It seems that compared with the plasma AVP concentration, CSF AVP is more related to the severity of tSAH.