The specific protective mechanism of mitophagy and Nrf2 in brain injury has not been fully clarified. This study aimed to reveal the effect of Nrf2 on hydraulic shock brain injury in mice, and explore its possible mechanism. Twenty-four Nrf2 knockout (Nrf2-/-) and wild-type mice (WT) of C57BL/6J were randomly divided into two groups: control group (C) and brain injury group (TBI). Hematoxylin-eosin staining (HE) assay was used for the histomorphological observation. The apoptotic state of brain tissue was detected by TUNEL. Mechanical damage in vitro models of glial cells were prepared. The wild-type (WT) and Nrf2 knockout (KO) mice were constructed to investigate the changes of mitophagy and apoptosis-related indicators by Western blotting. The experimental results showed that 24 h after TBI, the tissue structure was highly porous, the cells were highly edema, the neuronal space increased significantly, the neuron degeneration, and the cell vacuolation was obvious. Meanwhile, the number of apoptotic cells and the apoptosis rate of glial cells increased significantly. After injury, the relative expression of Parkin, Pink, Beclin and LC-3II proteins were significantly decreased in all mice. The protein expressions of Caspase3 and Caspase12 were significantly increased. However, in the TBI group, KO mice were more impaired than WT mice. In conclusion, Nrf2 plays a protective role by promoting mitophagy to inhibit apoptosis in the process of brain injury caused by hydraulic shock in mice, which provides a new idea for the effective treatment of brain injury.
Background: Optic nerve sheath diameter (ONSD) is a promising, noninvasive invasive intracranial pressure (ICP) measurement method. This study aims to analyze the differences in ONSD between the left and right eyeballs and the differences in ultrasonic measurement between the transverse and sagittal planes. Methods: Data from a total of 50 eligible patients with various types of brain injury who were admitted to our hospital from May 2019 to June 2021 were analyzed. An ONSD assessment was then performed using Philips B-mode ultrasound, measuring ONSD 3 mm posterior to the eyeballs. The left and right ONSDs in the transverse and sagittal planes were measured. Intraparenchymal fiber optic sensors and catheters were inserted into the ventricles and connected to an external pressure transducer to measure ICP. Results: A total of 164 sonographic measurements of ONSD were performed in 50 patients with brain injury in a prospective observational study. Statistically significant differences were found in ONSD between the transverse and sagittal planes. The difference in the left ONSD between the transverse and sagittal planes was 0.007 ± 0.030 cm (P = 0.003). The Spearman rank correlation test showed that the correlation coefficient between ICP and left/right ONSD in the transverse/sagittal planes was 0.495 vs 0.546 and 0.559 vs 0.605, respectively. The results showed that the areas under the curve of ONSD in the transverse and sagittal planes were 0.843 and 0.805, respectively. Medcalc software was used to compare the areas under the receiver operator characteristic curve, and the results showed that ONSD in the sagittal plane is generally better than in the transverse plane (P = 0.0145). Conclusions: This study found that ONSD in the sagittal plane is superior to the transverse plane regarding the comprehensive efficacy of ICP, and unilateral measurement is sufficient.
This study aims to detect whether the optic nerve sheath diameter (ONSD) can be used to dynamically monitor intracranial pressure (ICP). Adult patients undergoing invasive ICP monitoring on the day of admission are included in this study. For each patient, the ONSD is first measured in the supine position and then in the 30∘ head-up position. Subsequently, a dynamic test is conducted on 16 patients. The ONSD is measured in the supine position once a day for three consecutive days starting on the day of admission. There is a strong correlation between the ONSD and ICP values in the supine position on admission (r = 0.799), and when patients are changed from the supine to the 30∘ head-up position, the ICP and ONSD values decrease correspondingly. However, the change in ICP is not strongly correlated with the change in ONSD (r = 0.358). In the dynamic test, a good agreement between the ICP and ONSD only exists in three patients (18.8%), and three patients have completely different profiles for ICP and ONSD. These results suggest that the changes in the ONSD and ICP values are not closely correlated after dynamic observation. Therefore, measurement of the ONSD may not be a suitable tool to dynamically monitor ICP.
Hemorrhagic shock is associated with activation of renin-angiotensin system (RAS) and endoplasmic reticulum stress (ERS). Previous studies demonstrated that central RAS activation produced by various challenges sensitizes angiotensin (Ang) II-elicited hypertension and that ERS contributes to the development of neurogenic hypertension. The present study investigated whether controlled hemorrhage could sensitize Ang II-elicited hypertension and whether the brain RAS and ERS mediate this sensitization. Results showed that hemorrhaged (HEM) rats had a significantly enhanced hypertensive response to a slow-pressor infusion of Ang II when compared to sham HEM rats. Treatment with either angiotensin-converting enzyme (ACE) 1 inhibitor, captopril, or ACE2 activator, diminazene, abolished the HEM-induced sensitization of hypertension. Treatment with the ERS agonist, tunicamycin, in sham HEM rats also sensitized Ang II-elicited hypertension. However, blockade of ERS with 4-phenylbutyric acid in HEM rats did not alter HEM-elicited sensitization of hypertension. Either HEM or ERS activation produced a greater reduction in BP after ganglionic blockade, upregulated mRNA and protein expression of ACE1 in the hypothalamic paraventricular nucleus (PVN), and elevated plasma levels of Ang II but reduced mRNA expression of the Ang-(1-7) receptor, Mas-R, and did not alter plasma levels of Ang-(1-7). Treatment with captopril or diminazene, but not phenylbutyric acid, reversed these changes. No treatments had effects on PVN protein expression of the ERS marker glucose-regulated protein 78. The results indicate that controlled hemorrhage sensitizes Ang II-elicited hypertension by augmenting RAS prohypertensive actions and reducing RAS antihypertensive effects in the brain, which is independent of ERS mechanism.
Objective:To investigate the relationship between the origin of vertebral artery and the height of transverse foramen of cervical vertebra using three-dimensional CT angiography (CTA).Methods:The clinical data of 480 patients who underwent head, neck and upper chest CTA examinations from March 2017 to March 2019 at Department of Neurosurgery, the Second Hospital of Hebei Medical University were retrospectively analyzed. The images were transferred to the image post-processing workstation for bone and vascular reconstruction, and the origin and course of bilateral vertebral arteries and the height of the vertebral arteries entering the cervical vertebrae transverse foramen were documented. Patients with normal origin of the right vertebral artery were divided into groups C 4, C 5, and C 6 according to the height of vertebral artery entering transverse foramen of cervical vertebra. Ten cases were randomly selected from each group to measure the distance from the origin of right vertebral artery to the origin of right common carotid artery (L 1) and to the right thyroid cervical trunk (L 2). We calculated the relative position of the origin of vertebral artery with L1/(L 1+ L 2)×100%. Results:Among 480 patients, 457 cases (95.2%) had normal origins of bilateral vertebral arteries which were from the subclavian artery, and the other 23 cases (4.8%) had abnormal origins. Among them, the left vertebral artery originated from the aortic arch in 19 cases, and left vertebral artery originated from the left external carotid artery in 1 case; the right vertebral artery originated from the right common carotid artery in 3 cases, all of which were complicated with aberrant right subclavian artery. Among the 480 patients, 405 cases (84.4%) had bilateral vertebral arteries entering the C 6 transverse foramen. The remaining 75 (15.6%) had vertebral arteries entering the cervical transverse foramen with abnormal height, which was observed on the left side in 34 cases (left vertebral arteries entering transverse foramen of C 3, C 4, C 5, C 7 in 1 case, 4 cases, 24 cases and 4 cases respectively, and directly entering the foramen magnum in 1 case) and on the right side in 41 cases (right vertebral artery entering C 3, C 4 and C 5 in 1 case, 14 cases, 26 cases respectively). The height of vertebral artery entering transverse foramen of cervical vertebra was mostly abnormal when the origin of left vertebral artery was abnormal. In patients with abnormal vertebral artery origin, the left vertebral artery originating from the aortic arch accounted for the highest proportion (19/20), and most of the vertebral arteries entered the transverse foramen of cervical vertebra with abnormal height (18/19). The right vertebral artery originating from the right common carotid artery were complicated with aberrant right subclavian artery (3/3), and the height of vertebral artery entering transverse foramen of cervical vertebra was abnormal (3/3). In patients with normal vertebral artery origin, 96.7% (445/460) of left vertebral artery entered transverse foramen of cervical vertebra with normal height, and 92.0% (439/477) of the right vertebral artery entered transverse foramen of cervical vertebra with normal height. Comparison of patients with normal right vertebral artery origin in the 3 groups showed statistically significant differences in the relative position of the vertebral artery origin (C 4 group: 24.3±2.1 %, C 5 group: 47.9±6.6 %, and C 6 group: 77.7±1.7 %, H=20.178, P<0.001). Conclusions:In case of abnormal origins of vertebral arteries, the heights of vertebral arteries at the transverse foramen of cervical vertebra are mostly abnormal. When the relative position of origin of right vertebral artery is closer to the right common carotid artery, the height of right vertebral artery at the transverse foramen of cervical vertebra seems higher. When the relative origin of right vertebral artery is closer to the right thyroid cervical trunk, the height of right vertebral artery at the transverse foramen of cervical vertebra seems lower.
Objective To provide with our experience on intracranial aneurysm as a reference for clinician by summarizing the clinical epidemiologic characteristic and course of diagnosis and treatment on the disease. Methods It was accomplished that retrospective analysis for 473 cases of intracranial aneurysms admitted in our hospital from Jan-2003 to Jul-2007 to summarize clinical epidemiologic characteristic, clinical manifestation, results of diagnosis and treatment. statistical treatment was completed for all of this clinical data. Results The incidence of aneurismal subarachnoid hemorrhage has a peak at 50 ~ 59 years of age(33.83%), and 75.26% of those patients was at 40~69 years of age. In younger 40 years Groups, Male patients were more than female; but in elder 40 years Groups, status was opposite. There were an 1.17, 1.97-fold female predominance in patients of single-aneurysm and multi-aneurysm, respectively. Percentage of unruptured intracranial aneurysm in all patients was 2.54%. Of patients suffering from aneurysm rupture, constipation, agitation, insobriety, exertion and severe cough were common remote causes of aneurysm rupture, which was 66.59% of those;the cases complicated with one or more of hypertension, diabetes, excessive drinking and smoking was 51.99%. disappropriate lumbar puncture and external ventricular drainage possibly caused rebleeding of aneurysm, which was the rate of 16.67% in all of reasons. The rate of unfavourable prognosis for patients of first and multiple rupture was 19.89% and 38.89%, respectively. Favourable prognosis for patients of gradeⅠ~Ⅲ(Hunt Hess) in early(3 days), intermediate (3~10 days)and late clipping surgery (10 days) was no significant difference. But for cases of grade Ⅳ~Ⅴ, the result of early clipping operation was much better than that at intermediate-late stage(P=0.026). Conclusion The patients with ruptured intracranial aneurysm have a tendency to become younger. Some of female physiological characteristics maybe were one of the etiological factors for intracranial aneurysm. More unruptured aneurysms were found by filting high-risk groups and increasing the rate of final diagnosis at first break maybe were important measures to improve prognosis of the aneurismal patients. Lumbar puncture and external ventricular drainage should be avoided to be used for patients with untreated ruptured aneurysm. Timing of surgery was not matter cause of outcome in patients of grade Ⅰ to Ⅲ. But early operation could take more benefit for patients of grades Ⅳ to Ⅴ.
Objective To investigate the major factors affecting the prognosis of ruptured intracranial aneurysms so as to provide theoretical foundation for the treatment of intracranial aneurysm.Methods The clinical data of 794 cases with ruptured intracranial aneurysms in seven hospitals in Shijiazhuang between 2003 and 2007 were studied retrospectively.Prognostic factors were analyzed according to sex,age,Hunt-Hess classification,location and amount of aneurysms,time and methods of operation,hypertension and smoking.Univariate analysis of variance by χ2 test and multivariate analysis by multiple Logistic regression model were carried out to screen risk factors related to the prognosis of ruptured intracranial aneurysms.Results Univariate analysis showed that there was statistical significance of difference in Hunt-Hess grade(P0.0001),age(P0.0001) and hypertension(P=0.0226);multivariate Logistic regression analysis showed that Hunt-Hess grade(P0.0001,OR=34.854),age(P0.0001,OR=1.779) and hypertension(P=0.0057,OR=1.413) were related to the prognosis of ruptured intracranial aneurysms.Conclusion Hunt-Hess grade,age and hypertension are independent risk factors for the prognosis of ruptured intracranial aneurysms.The prognosis of patients with hypertension,more Hunt-Hess scores and aging over 60 is poorer.
Objective:To investigate the correlation between surgical timing and clinical prognosis on ruptured intracranial aneurysm.Methods:387 cases of ruptured intracranial aneurysms admitted in our hospital from Jan-2003 to Jul-2007,whom clipping operations had been completed on,were divided into gradeⅠ~ⅡGroup(283cases),grade ⅢGroup(75cases)and Ⅳ~ⅤGroup(29cases)classified on the base of the HuntHess grade on admission.Each group was then divided into early surgery subgroup defined as operation performed within three days after onset of subarachnoid hemorrhage,intermediate surgery subgroup as performed on day four to ten and late surgery subgroup as performed after day ten.The incidences of good outcomes(Glasgow Outcome Scale,GOS4),delayed ischemic neurological deficit(DIND)and hydrocephalus at patients' discharge were statistically analyzed among those subgroups.Results:The incidences of good outcomes for patients of grade Ⅰ~Ⅱin early,intermediate and late surgery subgroup were 90.2%(46/51),82.0%(41/50)and 83.5%(152/182),respectively.For patients of grade Ⅳ~Ⅴwere 46.2%(6/13),20.0%(1/5)and 0%(0/11),respectively.In patients of gradeⅠ~Ⅱand grade Ⅲ Group,there was no statistically difference in good outcomes,DIND and hydrocephalus among there subgroups.In patients of grade IV~V Group,the rat of good outcomes except other aspects in early surgery subgroup was significantly higher than that in non-early surgery group(P=0.026).Conclusion:Timing of surgery was not matter cause of outcome in patients of grade I to III.But early operation could take more benefit for patients of grade IV to V.