• Biomolecules & Therapeutics
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• v.30 no.1
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• pp.55-63
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• 2022

Oleanolic acid (OA), a natural pentacyclic triterpenoid, has been reported to exert protective effects against several neurological diseases through its anti-oxidative and anti-inflammatory activities. The goal of the present study was to evaluate the therapeutic potential of OA against acute and chronic brain injuries after ischemic stroke using a mouse model of transient middle cerebral artery occlusion (tMCAO, MCAO/reperfusion). OA administration immediately after reperfusion significantly attenuated acute brain injuries including brain infarction, functional neurological deficits, and neuronal apoptosis. Moreover, delayed administration of OA (at 3 h after reperfusion) attenuated brain infarction and improved functional neurological deficits during the acute phase. Such neuroprotective effects were associated with attenuation of microglial activation and lipid peroxidation in the injured brain after the tMCAO challenge. OA also attenuated NLRP3 inflammasome activation in activated microglia during the acute phase. In addition, daily administration of OA for 7 days starting from either immediately after reperfusion or 1 day after reperfusion significantly improved functional neurological deficits and attenuated brain tissue loss up to 21 days after the tMCAO challenge; these findings supported therapeutic effects of OA against ischemic stroke-induced chronic brain injury. Together, these findings showed that OA exerted neuroprotective effects against both acute and chronic brain injuries after tMCAO challenge, suggesting that OA is a potential therapeutic agent to treat ischemic stroke.

• Journal of Trauma and Injury
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• v.31 no.2
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• pp.51-57
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• 2018

Purpose: Patients with diffuse axonal injury experience various disabilities and have a high cost of treatment. Recent researches have revealed the underlying mechanism and pathogenesis of diffuse axonal injury. This study aimed to investigate the correlation between the radiological grading of diffuse axonal injury and the clinical outcomes of patients. Methods: From January 2011 to December 2016, among 294 patients with traumatic brain injury, 44 patients underwent magnetic resonance imaging (MRI). A total of 18 patients were enrolled in this study except for other cerebral injuries, such as cerebral hemorrhage or hypoxic brain damage. Demographic data, clinical data, and radiological findings were retrospectively reviewed. The grading of diffuse axonal injury was analyzed based on patient's MRI findings. Results: For the most severe diffuse axonal injury patients, prolonged intensive care unit (ICU) stay (p=0.035), hospital stay (p=0.012), and prolonged mechanical ventilation (p=0.030) were observed. However, there was no significant difference in healthcare-associated infection rates between MRI grading (p=0.123). Massive transfusion, initial hemoglobin and lactate levels, and MRI gradings were found to be highly significant in predicting the duration of unconsciousness. Conclusions: This study showed that patients with high grade diffuse axonal injury have prolonged ICU stays and significantly longer hospital stays. Deteriorated mental patients with high energy injuries should be evaluated to identify diffuse axonal injuries by using an appropriate imaging tool, such as MRI. It will be important to predict the duration of consciousness recovery using MRI scans.

• The Korean Journal of Physiology and Pharmacology
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• v.24 no.2
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• pp.165-171
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• 2020

Ischemic and traumatic brain injuries are the major acute central nervous system disorders that need to be adequately diagnosed and treated. To find biomarkers for these acute brain injuries, plasma levels of some specialized pro-resolving mediators (SPMs, i.e., lipoxin A4 [LXA4], resolvin [Rv] E1, RvE2, RvD1 and RvD2), CD59 and interleukin (IL)-6 were measured at 0, 6, 24, 72, and 168 h after global cerebral ischemic (GCI) and traumatic brain injuries (TBI) in rats. Plasma LXA4 levels tended to increase at 24 and 72 h after GCI. Plasma RvE1, RvE2, RvD1, and RvD2 levels showed a biphasic response to GCI; a significant decrease at 6 h with a return to the levels of the sham group at 24 h, and again a decrease at 72 h. Plasma CD59 levels increased at 6 and 24 h post-GCI, and returned to basal levels at 72 h post-GCI. For TBI, plasma LXA4 levels tended to decrease, while RvE1, RvE2, RvD1, and RvD2 showed barely significant changes. Plasma IL-6 levels were significantly increased after GCI and TBI, but with different time courses. These results show that plasma LXA4, RvE1, RvE2, RvD1, RvD2, and CD59 levels display differential responses to GCI and TBI, and need to be evaluated for their usefulness as biomarkers.

• Journal of Korean Neurosurgical Society
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• v.46 no.3
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• pp.215-220
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• 2009

Objective : Intraoperative ventriculostomy is widely adopted to make the slack brain. However, there are few reports about hemorrhagic or parenchymal injuries after ventriculostomy. We tried to analyze and investigate the incidence of these complications in a consecutive series of patients with aneurysmal subarachnoid hemorrhage (SAH). Methods : From September 2006 to June 2007, 43 patients underwent surgical clipping for aneurysmal SAH at our hospital. Among 43 patients, we investigated hemorrhagic or parenchymal injuries after intraoperative ventriculostomy using postoperative computed tomographic scan in 26 patients. After standard pterional craniotomy, ventriculostomy catheter was inserted perpendicular to the cortical surface along the bisectional imaginary line from Paine's point. Results : Hemorrhagic injuries were detected in 12 of 26 patients (46.2%). Mean systolic blood pressure during anesthesia was with in statistically significant parameter related to hemorrhage (p=0.006). On the other hand, parenchymal injuries were detected in 11 of 26 patients (42.3%). Female and the amount of infused mannitol during anesthesia showed statistically significant parameters related to parenchymal injury (p=0.005, 0.04, respectively). However, there were no ventriculostomy-related severe complications. Conclusion : In our series, hemorrhagic or parenchymal injuries after intraoperative ventriculostomy occurred more commonly than previously reported series in aneurysmal SAH patients. Although the clinical outcomes of complications are generally favorable, neurosurgeon must keep in mind the frequent occurrence of brain injury after intraoperative ventriculostomy in the acute stage of aneurysmal SAH.

• Biomolecules & Therapeutics
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• v.28 no.6
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• pp.512-518
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• 2020

Stroke is a leading cause of long-term disability in ischemic survivors who are suffering from motor, cognitive, and memory impairment. Previously, we have reported suppressing LPA₅ activity with its specific antagonist can attenuate acute brain injuries after ischemic stroke. However, it is unclear whether suppressing LPA₅ activity can also attenuate chronic brain injuries after ischemic stroke. Here, we explored whether effects of LPA₅ antagonist, TCLPA5, could persist a longer time after brain ischemic stroke using a mouse model challenged with tMCAO. TCLPA5 was administered to mice every day for 3 days, starting from the time immediately after reperfusion. TCLPA5 administration improved neurological function up to 21 days after tMCAO challenge. It also reduced brain tissue loss and cell apoptosis in mice at 21 days after tMCAO challenge. Such long-term neuroprotection of TCLPA5 was associated with enhanced neurogenesis and angiogenesis in post-ischemic brain, along with upregulated expression levels of vascular endothelial growth factor. Collectively, results of the current study indicates that suppressing LPA₅ activity can provide long-term neuroprotection to mice with brain ischemic stroke.

• Toxicological Research
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• v.17 no.2
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• pp.73-82
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• 2001

The incidence and distribution of necrotic and apoptotic neural cells, and activated astrocytes in the brain of rats intoxicated intra peritoneally with diisopropylfluorophosphate were investigated. Pyridostigmine bromide (0.1 mg/kg) and atropine methylnitrate (20 mg/kg) were pretreated intramuscularly 30 min and 10 min, respectively, prior to diisopropylfluorophosphate (4-10 mg/kg) administration. Diisopropylfluorophosphate induced severe limbic seizures, early necrotic and delayed apoptotic brain injuries, and rapid astrocytic responses. The necrosis, which was closely related to seizure intensity, was observed as early as 1 hr after intoxication predominently in hippocampal pyramidal cells, cerebellar Purkinje cells and neurons in pyriform/entorhinal cortices, showing malacia of neurophils. In contrast, apoptosis started to appear 12 hr after intoxication in neurons in thalamus, amygdala and neocortex, and ephendymal cells surrounding the 4th ventricle. Since marked apoptosis was induced in rats exhibiting relatively-low seizure intensity, the degree of necrosis and apoptosis was shifted to each type of injury according to the seizure intensity. Activated astrocytes, observed within 1 hr along the limbic system, were suggested to affect the neural injury patterns by producing high level of nitric oxide. However, the distribution of activated astrocytes was not in parallel with those of necrotic or apoptotic injuries, implying that the astrocytic responses resulted from seizure activity rather than neural injuries. Furthermore, astrocytes in malacic tissues disappeared during the severe limbic seizures. Therefore, it would be one of the cautionary notes on the expression of glial fibrillary acidic protein in astrocytes as a biochemical marker of brain injuries following acute exposure to organophosphates.

• Journal of Korean Neurosurgical Society
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• v.65 no.5
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• pp.680-687
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• 2022

Objective : The influence of moderate-to-severe traumatic brain injury (TBI) on acute pulmonary injury is well established, but the association between acute pulmonary injury and mild TBI has not been well studied. Here, we evaluated the histological changes and fluctuations in inflammatory markers in the lungs to determine whether an acute pulmonary inflammatory response occurred after mild TBI. Methods : Mouse models of mild TBI (n=24) were induced via open-head injuries using a stereotaxic impactor. The brain and lungs were examined 6, 24, and 72 hours after injury and compared to sham-operated controls (n=24). Fluoro-Jade B staining and Astra blue and hematoxylin staining were performed to assess cerebral neuronal degeneration and pulmonary histological architecture. Quantitative real-time polymerase chain reaction analysis was done to measure inflammatory cytokines. Results : Increased neuronal degeneration and the mRNA expression of interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-10, and transforming growth factor (TGF)-β were observed after mild TBI. The IL-6, TNF-α, and TGF-β levels in mice with mild TBI were significantly different compared to those of sham-operated mice 24 hours after injury, and this was more pronounced at 72 hours. Mild TBI induced acute pulmonary interstitial edema with cell infiltration and alveolar morphological changes. In particular, a significant infiltration of mast cells was observed. Among the inflammatory cytokines, TNF-α was significantly increased in the lungs at 6 hours, but there was no significant difference 24 and 72 hours after injury. Conclusion : Mild TBI induced acute pulmonary interstitial inflammation and alveolar structural changes, which are likely to worsen the patient's prognosis.

• Journal of Trauma and Injury
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• v.35 no.1
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• pp.43-45
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• 2022

Epidural hematoma (EDH) can sometimes be life-threatening, although small-volume EDHs can resolve spontaneously like other intracranial hematomas. However, in rare cases, EDH can transform into a chronic form instead of disappearing. In contrast to subdural hematoma, there is no agreed-upon definition or treatment of chronic EDH. A 41-year-old male patient with acute EDH in the bilateral paravertical area due to partial rupture of the sagittal sinus was operated first, and then remnant contralateral hematoma was treated conservatively. One month after surgery, he showed hemiparesis, and brain imaging revealed chronic EDH at the location of the remnant acute hematoma. We performed surgery again to treat chronic EDH through a large craniotomy. Although many cases of EDH are self-limited, clinicians must keep in mind that some cases of EDH, especially those of venous origin and arising in young people, can become chronic and require surgical treatment.

• Journal of Korean Neurosurgical Society
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• v.64 no.2
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• pp.255-260
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• 2021

Objective : We aimed to investigate the presence of brachial plexus injury (BPI) in traumatic brain injury (TBI) patients and to draw attention to BPI, which can be overlooked by physicians in TBI patients. Methods : The study was designed retrospectively by examining the files of 58 patients with moderate to severe TBI to investigate coexistence of TBI and BPI. Results : BPI was detected in six of 58 TBI patients (10.3%). BPI was detected after an average 116 days from the initial injury. Three patients had lower trunk BPI and three patients had panplexopathy. Conclusion : Diagnosis of BPI in patients with TBI is delayed in the acute period of injury. The clinicians should keep in mind that BPIs may occur and remain undiagnosed in patients with TBI.

• Journal of Korean Neurosurgical Society
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• v.54 no.2
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• pp.145-147
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• 2013

We present a case of acute hydrocephalus secondary to cervical spinal cord injury in a patient with diffuse ossification of the posterior longitudinal ligament (OPLL). A 75-year-old male patient visited the emergency department with tetraparesis and spinal shock. Imaging studies showed cervical spinal cord injury with hemorrhage and diffuse OPLL from C1 to C4. We performed decompressive laminectomy and occipitocervical fusion. Two days after surgery, his mental status had deteriorated to drowsiness with dilatation of the right pupil. Findings on brain computed tomography revealed acute hydrocephalus and subarachnoid hemorrhage in the cerebellomedullary cistern, therefore, extraventricular drainage was performed immediately. Acute hydrocephalus as a complication of cervical spine trauma is rare, however, it should be considered if the patient shows deterioration of neurologic symptoms.