More research needed, but is your doctor and hospital going to do one damn thing about that? Or just sit on their asses doing nothing?
Reasons for needing this in here:
Butylphthalide Combined With Conventional Treatment Attenuates MMP-9 Levels and Increases VEGF Levels in Patients With Stroke: A Prospective Cohort Study
Yingqiong Xiong1,2, 
Shaomin Cheng- 1Department of Neurology, the First Affiliated Hospital of Nanchang University, Nanchang, China
- 2Department of Neurology, Jiangxi People's Hospital, Nanchang, China
- 3School of Chinese Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, China
Background and Purpose: Butylphtalide increases the vascular endothelial growth factor (VEGF) and decreases matrix metalloproteinase (MMP)-9 in animal models of stroke and might be of use in the management of stroke. To explore whether butylphthalide combined with conventional treatment can change the levels of MMP-9 and VEGF and the National Institutes of Health Stroke Scale (NIHSS) scores of patients with stroke.
Methods: This was a prospective cohort study involving inpatients admitted to the Jiangxi Provincial People's Hospital (January–June 2019) due to acute cerebral infarction. The patients received conventional treatments with or without butylphthalide. The changes in the NIHSS scores were compared between groups. Plasma MMP-9 and VEGF were measured by enzyme-linked immunosorbent assay.
Results: A total of 24 patients were included in the conventional treatment group and 46 in the butylphthalide group. The butylphthalide group showed lower MMP-9 (130 ± 59 vs. 188 ± 65, p = 0.001) and higher VEGF (441 ± 121 vs. 378 ± 70, p = 0.034) levels on day 6 compared with the conventional treatment group. The changes in MMP-9 and VEGF were significant, starting on day 3 in the butylphthalide group but on day 6 in the conventional treatment group. There were no differences between the two groups in the NIHSS scores at admission and at discharge (p > 0.05). The overall response rate was higher in the butylphthalide group compared with the conventional treatment group (63.0 vs. 37.5%, p = 0.042).
Conclusion: Butylphthalide combined with conventional treatment can decrease MMP-9 levels and increase VEGF levels. The patients showed the reduced NIHSS scores, possibly suggesting some improvement in prognosis after stroke. Still, the conclusions need to be confirmed in a larger sample and in different etiological subtypes of stroke.
Introduction
A stroke is an episode of acute neurological dysfunction from either ischemic infarction or a collection of blood within the brain or ventricular system with a resultant focal injury of the central nervous system (CNS) (1). Ischemic strokes (80–87% of strokes) result from cardioembolism (often from atrial fibrillation), large artery atherosclerosis (embolus or thrombosis), small vessel occlusion (lacunar), or systemic hypoperfusion (1). The estimated global incidence of stroke is 2–3 per 1,000 person-years, with older patients and patients with carotid artery stenosis or atrial fibrillation having the highest risk (1, 2). The mortality due to stroke every year in China accounts for nearly one-third of the total stroke-related deaths worldwide (3). Stroke disease is the main cause of non-traumatic disability and death in China (3). In Jiangxi Province, the incidence of cerebrovascular diseases is higher than in the other provinces of China, with ischemic stroke being predominant (about 73.5%) (4). The acute management of stroke includes blood pressure management, airway support, maintaining blood glucose levels, thrombolytics, endovascular therapy, aspirin, and decompressive surgery (2). In China, complementary traditional Chinese medicine (TCM) is also used for acute stroke management (5, 6).
Matrix metalloproteinase (MMP)-9, also called gelatinase B, is the MMP with the highest expression after hypoxic-ischemic changes and is closely related to the occurrence and development of cerebral infarction (7–10). Normally, its expression in the brain is low, and it is present in the form of an inactive zymogen (7–10). During the inflammatory responses of brain ischemia and hypoxia, the white blood cells, microglia, and astrocytes can produce MMP-9, and the MMP-9 levels are closely associated with the severity of cerebral infarction (7–10). Other studies have also shown that elevated MMP-9 levels are present both in the infarcted tissues and the tissues around the infarction, indicating that MMP-9 might play a role in the expansion of the infarct size (11–13).
The vascular endothelial growth factor (VEGF)-A is the most abundant member of the VEGF family, and it is involved in angiogenesis, promoting neovascularization (14). VEGF is involved in many processes such as atherosclerosis, cerebral edema, arteriogenesis, neuroprotection, neurogenesis, angiogenesis, brain, and vascular repair after ischemia (14–16). Normally, vascular endothelial cells, as the target cells of VEGF, cannot promote VEGF expression, but under pathological states, the concentration of VEGF can change rapidly, and increased VEGF levels are observed after stroke (17, 18).
Butylphthalide is a novel drug independently developed by China to treat cerebral infarction, which includes dl-3-n-butylphthalide (NBP) as the main active component (C12H14O2). It is a phthalide, an oily liquid with a taste of celery. It has the same structure as the natural substance levorotatory butylphthalide and is a synthetic racemic mixture. It is present in TCM ingredients such as chuanxiong (Ligusticum chuanxiong hort), Chinese lovage, and Chinese angelica, among others. Butylphthalide is an important candidate for the management of neurologic diseases by favoring the reconstruction of the microcirculation and protecting the mitochondrial functions (19, 20). Previous studies showed that butylphthalide improves the local microcirculation, increases blood perfusion, and increases the number of capillaries in ischemic brain areas (21–25). Butylphthalide also increases vasodilation and inhibits platelet aggregation (26). NBP can inhibit thrombus formation (27). One study showed that butylphthalide increases VEGF expression in animal models of stroke (24). Another animal study showed that butylphthalide decreases poststroke inflammation and MMP-9 expression (28). The effects of butylphthalide on VEGF and MMP-9 have to be confirmed in humans.
Therefore, this study aims to explore whether butylphthalide combined with conventional treatment can change the levels of MMP-9 and VEGF and the National Institutes of Health Stroke Scale (NIHSS) scores of patients with stroke and improve their prognosis. The results could provide data for the eventual inclusion of butylphthalide in routine stroke management.
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