Search Results

You are looking at 1 - 10 of 27 items for

  • Author or Editor: Yi Yang x
Clear All Modify Search
Full access

Gary A. Rosenberg and Yi Yang

✓Cerebral ischemia causes cell swelling and breakdown of the blood–brain barrier (BBB). Cytotoxic edema results from energy failure, and vasogenic edema occurs when the blood vessels are damaged. Proteases and free radicals are the end result of a molecular injury cascade. Matrix metalloproteinases (MMPs) are a gene family of extracellular matrix-degrading enzymes that disrupt the BBB. Tight junction proteins (TJPs), occludin and claudin-5, which form the endothelial barrier, are vulnerable to attack by MMPs. Basal lamina proteins, such as fibronectin, laminin, and heparan sulfate, are also degraded by MMPs. Reperfusion injury leads to a biphasic opening of the BBB, with the early opening occurring several hours after the onset of reperfusion due to activation of the constitutive enzyme gelatinase A (MMP-2). This initial opening is transient and followed 24 to 48 hours later by more intense damage to the blood vessel, which is associated with the expression and activation of gelatinase B (MMP-9) and stromelysin-1 (MMP-3). Synthetic MMP inhibitors restore the early integrity of the BBB but are ineffective in the later opening. Because these inhibitors block MMPs involved in angiogenesis and neurogenesis, they also slow recovery. The challenge is to identify agents that will protect the BBB, blocking vasogenic edema without interfering with recovery.

Restricted access

Yi Yang, Qiu Li, Marian T. Nakada, Tao Yang and Ashfaq Shuaib

Object. Antagonists of the glycoprotein IIb/IIIa (GPIIb/IIIa) receptor complex are currently used for the treatment of acute coronary syndromes. The platelet GPIIb/IIIa mediates platelet aggregation, and blocking this receptor complex can reduce or prevent arterial thrombosis. To study the recanalization efficacy of a GPIIb/IIIa antagonist in treating cerebral ischemia, we investigated the therapeutic effects of murine 7E3 F(ab′)2 in a focal embolic cerebral ischemia model in rats.

Methods. Focal cerebral ischemia was produced by introducing an autologous thrombus into the right side of the middle cerebral artery (MCA). Thirty male Wistar rats were randomly divided into three groups of 10 rats each: control, 7E3 F(ab′)2 administered 1 hour postischemia, and 7E3 F(ab′)2 administered 3 hours postischemia. Animals in the therapeutic groups received intravenous infusion of 6 mg/kg 7E3 F(ab′)2 at 1 or 3 hours following cerebral embolization. Brain infarct volume, neurobehavioral scores, duration of bleeding, and findings on angiograms of the MCA (before and after infusion) were assessed in all animals.

Angiographic evaluation revealed full MCA recanalization in three of 10 animals in each 7E3 F(ab′)2 treatment group. Animals in these groups exhibited a significant reduction in infarct volume when compared with animals in the control group: 1) infarct volume 1 hour postischemia, 22 ± 13.9% (p = 0.005); 2) infarct volume 3 hours postischemia, 22.1 ± 14.8% (p = 0.008); and 3) infarct volume in control animals, 42.4 ± 16%. Postischemia treatment with 7E3 F(ab′)2 also improved the animal's neurobehavioral performance. The duration of bleeding significantly increased by more than two times, but there was no associated increase in intracerebral hemorrhage in any group.

Conclusions. On the basis of their findings, the authors conclude that murine 7E3 F(ab′)2 is a potent and safe antiplatelet agent in this experimental focal embolic cerebral ischemia model. Neuronal lesions were significantly reduced when the treatment was delayed up to 3 hours.

Full access

Xiang-Ming Li, Jian-Tao Yang, Yi Hou, Yi Yang, Ben-Gang Qin, Guo Fu and Li-Qiang Gu

OBJECT

Donor-side morbidity associated with contralateral C-7 (CC7) nerve transfer remains controversial. The purpose of this study was to evaluate functional deficits in the donor limb resulting from prespinal route CC7 nerve transfer.

METHODS

A total of 63 patients were included. Forty-one patients had undergone CC7 nerve transfer surgery at least 6 months previously and were assigned to one of 2 groups based on the duration of postoperative follow-up. Group 1 (n = 21) consisted of patients who had undergone surgery between 6 months and 2 years previously, and Group 2 (n = 20) consisted of patients who had undergone surgery more than 2 years previously. An additional 22 patients who underwent CC7 nerve transfer surgery later than those in Groups 1 and 2 were included as a control group (Group 3). Results of preoperative testing in these patients and postoperative testing in Groups 1 and 2 were compared. Testing included subjective assessments and objective examinations. An additional 3 patients had undergone surgery more than 6 months previously but had severe motor weakness and were therefore evaluated separately; these 3 patients were not included in any of the study groups.

RESULTS

The revised Short-Form McGill Pain Questionnaire (SF-MPQ-2) was the only subjective test that showed a significant difference between Group 3 and the other 2 groups, while no significant differences were found in objective sensory, motor, or dexterity outcomes. The interval from injury to surgery for patients with a normal SF-MPQ-2 score in Groups 1 and 2 was significantly less than for those with abnormal SF-MFQ-2 scores (2.4 ± 1.1 months vs 4.6 ± 2.9 months, p = 0.002). The 3 patients with obvious motor weakness showed a tendency to gradually recover.

CONCLUSIONS

Although some patients suffered from long-term sensory disturbances, resection of the C-7 nerve had little effect on the function of the donor limb. Shortening preoperative delay time can improve sensory recovery of the donor limb.

Full access

Hao-Li Liu, Hung-Wei Yang, Mu-Yi Hua and Kuo-Chen Wei

Malignant glioma is a severe primary CNS cancer with a high recurrence and mortality rate. The current strategy of surgical debulking combined with radiation therapy or chemotherapy does not provide good prognosis, tumor progression control, or improved patient survival. The blood-brain barrier (BBB) acts as a major obstacle to chemotherapeutic treatment of brain tumors by severely restricting drug delivery into the brain. Because of their high toxicity, chemotherapeutic drugs cannot be administered at sufficient concentrations by conventional delivery methods to significantly improve long-term survival of patients with brain tumors. Temporal disruption of the BBB by microbubble-enhanced focused ultrasound (FUS) exposure can increase CNS-blood permeability, providing a promising new direction to increase the concentration of therapeutic agents in the brain tumor and improve disease control. Under the guidance and monitoring of MR imaging, a brain drug-delivery platform can be developed to control and monitor therapeutic agent distribution and kinetics. The success of FUS BBB disruption in delivering a variety of therapeutic molecules into brain tumors has recently been demonstrated in an animal model. In this paper the authors review a number of critical studies that have demonstrated successful outcomes, including enhancement of the delivery of traditional clinically used chemotherapeutic agents or application of novel nanocarrier designs for actively transporting drugs or extending drug half-lives to significantly improve treatment efficacy in preclinical animal models.

Restricted access

Ho Jun Yi, Jae Hoon Sung, Dong Hoon Lee, Seung Ho Yang and Jae Taek Hong

OBJECTIVE

Volume perfusion CT (VPCT) with added CT angiography (CTA)–like reconstruction from VPCT source data (VPCTA) can reveal multiple intracranial parameters. The authors examined the usefulness of VPCTA in terms of reducing the in-hospital time delay for mechanical thrombectomy.

METHODS

A total of 180 patients who underwent mechanical thrombectomy at the authors’ institution between January 2014 and March 2017 were divided into 2 groups: a CTA-based thrombectomy decision group (group 1: CTA) and a VPCTA-based decision group (group 2: VPCTA). Multiple time interval categories (from symptom onset to groin puncture, from hospital arrival to groin puncture, procedure time, from symptom onset to reperfusion, and from hospital arrival to reperfusion) were reviewed. All patients underwent clinical assessment with the National Institutes of Health Stroke Scale score and the modified Rankin Scale, and radiological results were evaluated by the Thrombolysis in Cerebral Infarction score.

RESULTS

In all of the time interval categories except for procedure time, the VPCTA group showed a significantly shorter in-hospital time delay during the prethrombectomy period than did the CTA group. The 3-month modified Rankin Scale score was significantly lower in the VPCTA group (2.8) compared with the CTA group (3.5) (p = 0.003). However, there were no statistically significant differences between the 2 groups in the other clinical and radiological outcomes.

CONCLUSIONS

Compared with CTA, VPCTA significantly reduced the in-hospital time delay during the prethrombectomy period.

Restricted access

Ho Jun Yi, Jae Hoon Sung, Dong Hoon Lee, Seung Ho Yang and Jae Taek Hong

OBJECTIVE

Volume perfusion CT (VPCT) with added CT angiography (CTA)–like reconstruction from VPCT source data (VPCTA) can reveal multiple intracranial parameters. The authors examined the usefulness of VPCTA in terms of reducing the in-hospital time delay for mechanical thrombectomy.

METHODS

A total of 180 patients who underwent mechanical thrombectomy at the authors’ institution between January 2014 and March 2017 were divided into 2 groups: a CTA-based thrombectomy decision group (group 1: CTA) and a VPCTA-based decision group (group 2: VPCTA). Multiple time interval categories (from symptom onset to groin puncture, from hospital arrival to groin puncture, procedure time, from symptom onset to reperfusion, and from hospital arrival to reperfusion) were reviewed. All patients underwent clinical assessment with the National Institutes of Health Stroke Scale score and the modified Rankin Scale, and radiological results were evaluated by the Thrombolysis in Cerebral Infarction score.

RESULTS

In all of the time interval categories except for procedure time, the VPCTA group showed a significantly shorter in-hospital time delay during the prethrombectomy period than did the CTA group. The 3-month modified Rankin Scale score was significantly lower in the VPCTA group (2.8) compared with the CTA group (3.5) (p = 0.003). However, there were no statistically significant differences between the 2 groups in the other clinical and radiological outcomes.

CONCLUSIONS

Compared with CTA, VPCTA significantly reduced the in-hospital time delay during the prethrombectomy period.

Restricted access

Haichun Liu, Wenliang Wu, Yi Li, Jinwei Liu, Kaiyun Yang and Yunzhen Chen

Object

During the past decades, lumbar fusion has increasingly become a standard treatment for degenerative spinal disorders. However, it has also been associated with an increased incidence of adjacent-segment degeneration (ASD). Previous studies have reported less ASD in anterior fusion surgeries; thus, the authors hypothesized that the integrity of the posterior complex plays an important role in ASD. This study was designed to investigate the effect of the posterior complex on adjacent instability after lumbar instrumentation and the development of ASD.

Methods

To evaluate different surgical interventions, 120 patients were randomly allocated into 3 groups of 40 patients each who were statistically similar with respect to demographic and clinical data. Patients in Group A were allocated for facet joint resection and L4–5 fusion, Group B for semilaminectomy and fusion, and Group C for complete laminectomy and fusion. All of the patients were followed up for 5–7 years (mean 5.9 years). The disc height, intervertebral disc angle, dynamic intervertebral angular range of motion (ROM), L3–4 slip, and the total lordosis angle were each measured before the operation and at the final follow-up. The Japanese Orthopaedic Association (JOA) score was determined before surgery and at the final follow-up to evaluate the clinical results.

Results

Among the 3 groups, no significant differences were detected in all clinical and demographic assessments before surgery. At 3 months after surgery, the JOA score of all groups improved significantly and showed no significant differences among the groups. At the final follow-up, Group C had a significantly (p < 0.05) lower JOA score than the other 2 groups. Moreover, the disc height and total lumbar lordosis in patients of Group C were significantly decreased compared with disc height and total lumbar lordosis in the other 2 groups. In contrast, disc angle, dynamic angular ROM, and listhesis were significantly higher in Group C than in the other 2 groups. Twenty-four patients showed signs of ASD after the operation (3 patients in Group A, 4 in B, and 17 in C). The number of patients in Group C showing ASD was significantly different from that in Groups A and B.

Conclusions

During follow-up for 6 years, a significantly higher number of patients with ASD were noted in the complete-laminectomy group. The number of reoperations for treating ASD was much higher in this patient group than in the patients undergoing facet joint resection and L4–5 fusion or semilaminectomy and fusion. Therefore, preserving the posterior complex as much as possible during surgery plays an important role in preventing ASD and in reducing the reoperation rate.

Restricted access

Yi Yang, Qiu Li, Tao Yang, Munawar Hussain and Ashfaq Shuaib

Object. A novel postsynaptic antagonist of N-methyl-d-aspartate (NMDA) receptors, CP-101,606-27 may attenuate the effects of focal ischemia. In current experiments, the authors investigated its neuroprotective effect alone and in combination with recombinant tissue plasminogen activator (rt-PA) in thromboembolic focal cerebral ischemia in rats.

Methods. Forty-eight male Wistar rats underwent embolization of the right middle cerebral artery to produce focal cerebral ischemia. After random division into six groups (eight rats in each group), animals received: vehicle; low-dose (LD) CP-101,606-27, 14.4 mg/kg; high-dose (HD) CP-101,606-27, 28.8 mg/kg; rt-PA, 10 mg/kg; low-dose combination (LDC) CP-101,606-27, 14.4 mg/kg plus rt-PA, 10 mg/kg; or high-dose combination (HDC) CP-101,606-27, 28.8 mg/kg plus rt-PA, 10 mg/kg) 2 hours after induction of embolic stroke. Animals were killed 48 hours after the onset of focal ischemia. Brain infarction volume, neurobehavioral outcome, poststroke seizure activity, poststroke mortality, and intracranial hemorrhage incidence were observed and evaluated. Compared with vehicle-treated animals (39.4 ± 8.6%) 2 hours posttreatment with CP-101,606-27 or rt-PA or in combination a significant reduction in the percentage of brain infarct volume was seen (LD CP-101,606-27: 20.8 ± 14.3%, p < 0.05; HD CP-101,606-27: 10.9 ± 3.2%, p < 0.001; rt-PA: 21.1 ± 7.3%, p < 0.05; LDC, 18.6 ± 11.5%, p < 0.05; and HDC: 15.2 ± 10.1%, p < 0.05; compared with control: 39.4 ± 8.6%). Combination of CP-101,606-27 with rt-PA did not show a significantly enhanced neuroprotective effect. Except for the control and LDC treatment groups, neurobehavioral outcome was significantly improved 24 hours after embolic stroke in animals in all other active therapeutic groups receiving CP-101,606-27 or rt-PA or in combination. The authors also observed that treatment with HD CP-101,606-27 decreased poststroke seizure activity.

Conclusions. The data in this study suggested that postischemia treatment with CP-101,606-27 is neuroprotective in the current stroke model; however, the authors also note that although rt-PA may offer modest protection when used alone, combination with CP-101,606-27 did not appear to enhance its effects.

Restricted access

Liang Li, Jiantao Yang, Bengang Qin, Honggang Wang, Yi Yang, Jintao Fang, Gang Chen, Xiaolin Liu, Zhehui Tu and Liqiang Gu

OBJECTIVE

Human acellular nerve allograft applications have increased in clinical practice, but no studies have quantified their influence on reconstruction outcomes for high-level, greater, and mixed nerves, especially the brachial plexus. The authors investigated the functional outcomes of human acellular nerve allograft reconstruction for nerve gaps in patients with brachial plexus injury (BPI) undergoing contralateral C7 (CC7) nerve root transfer to innervate the upper trunk, and they determined the independent predictors of recovery in shoulder abduction and elbow flexion.

METHODS

Forty-five patients with partial or total BPI were eligible for this retrospective study after CC7 nerve root transfer to the upper trunk using human acellular nerve allografts. Deltoid and biceps muscle strength, degree of shoulder abduction and elbow flexion, Semmes-Weinstein monofilament test, and static two-point discrimination (S2PD) were examined according to the modified British Medical Research Council (mBMRC) scoring system, and disabilities of the arm, shoulder, and hand (DASH) were scored to establish the function of the affected upper limb. Meaningful recovery was defined as grades of M3–M5 or S3–S4 based on the scoring system. Subgroup analysis and univariate and multivariate logistic regression analyses were conducted to identify predictors of human acellular nerve allograft reconstruction.

RESULTS

The mean follow-up duration and the mean human acellular nerve allograft length were 48.1 ± 10.1 months and 30.9 ± 5.9 mm, respectively. Deltoid and biceps muscle strength was grade M4 or M3 in 71.1% and 60.0% of patients. Patients in the following groups achieved a higher rate of meaningful recovery in deltoid and biceps strength, as well as lower DASH scores (p < 0.01): age < 20 years and age 20–29 years; allograft lengths ≤ 30 mm; and patients in whom the interval between injury and surgery was < 90 days. The meaningful sensory recovery rate was approximately 70% in the Semmes-Weinstein monofilament test and S2PD. According to univariate and multivariate logistic regression analyses, age, interval between injury and surgery, and allograft length significantly influenced functional outcomes.

CONCLUSIONS

Human acellular nerve allografts offered safe reconstruction for 20- to 50-mm nerve gaps in procedures for CC7 nerve root transfer to repair the upper trunk after BPI. The group in which allograft lengths were ≤ 30 mm achieved better functional outcome than others, and the recommended length of allograft in this procedure was less than 30 mm. Age, interval between injury and surgery, and allograft length were independent predictors of functional outcomes after human acellular nerve allograft reconstruction.

Restricted access

He Xiao-Sheng, Yi Sheng-Yu, Zhang Xiang, Fei Zhou, Zhang Jian-Ning and Yang Li-Sun

Object. The authors investigated the ramifications of producing diffuse axonal injury (DAI) by lateral head rotation in a rat model.

Methods. Using a special injury-producing device, the rat's head was rapidly rotated 90° in the coronal plane at an angular velocity of at least 753.13 rad/second and an angular acceleration of at least 1.806 × 105 rad/second2; the rotation was complete within 2.09 msec. There were no statistically significant changes in PO2, PCO2, pH, or blood pressure values at 5, 15, or 60 minutes after head rotation compared with their respective preinjury baseline values. The rats exhibited posttraumatic behavior suppression for an average of 12.6 minutes. The mortality rate was 17%. The rats that survived had diffuse subarachnoid hemorrhage around the brainstem and upper cervical cord, but no obvious brain contusion. In sections stained with silver or hematoxylin and eosin, axonal swelling and bulblike protrusions at the axonal axis were observed in the medulla oblongata, midbrain, upper cervical cord, and corpus callosum between 6 hours and 144 hours postinjury. The axonal injuries were most severe in the brainstem and were accompanied by parenchymal bleeding. The density of bulblike axonal protrusions peaked 6 hours postinjury in the medulla oblongata and 24 hours postinjury in the midbrain.

Conclusions. Rapid lateral head rotation can produce DAI characterized by severe damage to the rat brainstem.