Exploring the Role of MMP-9 and MMP-9/TIMP-1 Ratio in Subacute Stroke Recovery: A Prospective Observational Study.

Despite the significant changes that unfold during the subacute phase of stroke, few studies have examined recovery abilities during this critical period. As neuroinflammation subsides and tissue degradation diminishes, the processes of neuroplasticity and angiogenesis intensify. An important factor in brain physiology and pathology, particularly neuroplasticity, is matrix metalloproteinase 9 (MMP-9). Its activity is modulated by tissue inhibitors of metalloproteinases (TIMPs), which impede substrate binding and activity by binding to its active sites. Notably, TIMP-1 specifically targets MMP-9 among other matrix metalloproteinases (MMPs). Our present study examines whether MMP-9 may play a beneficial role in psychological functions, particularly in alleviating depressive symptoms and enhancing specific cognitive domains, such as calculation. It appears that improvements in depressive symptoms during rehabilitation were notably linked with baseline MMP-9 plasma levels (r = -0.36, p = 0.025), and particularly so with the ratio of MMP-9 to TIMP-1, indicative of active MMP-9 (r = -0.42, p = 0.008). Furthermore, our findings support previous research demonstrating an inverse relationship between pre-rehabilitation MMP-9 serum levels and post-rehabilitation motor function. Crucially, our study emphasizes a positive correlation between cognition and motor function, highlighting the necessity of integrating both aspects into rehabilitation planning. These findings demonstrate the potential utility of MMP-9 as a prognostic biomarker for delineating recovery trajectories and guiding personalized treatment strategies for stroke patients during the subacute phase.

Circulating Serum VEGF, IGF-1 and MMP-9 and Expression of Their Genes as Potential Prognostic Markers of Recovery in Post-Stroke Rehabilitation-A Prospective Observational Study.

The key period in post-stroke recovery is the first three months due to the high activity of spontaneous and therapeutic-induced processes related to neuroplasticity, angiogenesis and reperfusion. Therefore, the present study examines the expression of VEGF, IGF-1 and MMP-9 proteins and their genes to identify biomarkers that can prognose brain repair ability and thus estimate the outcome of stroke. It also identifies possible associations with clinical scales, including cognitive assessment and depression scales. The study group comprised 32 patients with moderate ischemic stroke severity, three to four weeks after incident. The results obtained after three-week hospitalization indicate a statistically significant change in clinical parameter estimations, as well as in MMP9 and VEGF protein and mRNA expression, over the rehabilitation process. Our findings indicate that combined MMP9 protein and mRNA expression might be a useful biomarker for cognitive improvement in post-stroke patients, demonstrating 87% sensitivity and 71% specificity (p < 0.0001).

Neuroimaging Techniques as Potential Tools for Assessment of Angiogenesis and Neuroplasticity Processes after Stroke and Their Clinical Implications for Rehabilitation and Stroke Recovery Prognosis.

Stroke as the most frequent cause of disability is a challenge for the healthcare system as well as an important socio-economic issue. Therefore, there are currently a lot of studies dedicated to stroke recovery. Stroke recovery processes include angiogenesis and neuroplasticity and advances in neuroimaging techniques may provide indirect description of this action and become quantifiable indicators of these processes as well as responses to the therapeutical interventions. This means that neuroimaging and neurophysiological methods can be used as biomarkers-to make a prognosis of the course of stroke recovery and define patients with great potential of improvement after treatment. This approach is most likely to lead to novel rehabilitation strategies based on categorizing individuals for personalized treatment. In this review article, we introduce neuroimaging techniques dedicated to stroke recovery analysis with reference to angiogenesis and neuroplasticity processes. The most beneficial for personalized rehabilitation are multimodal panels of stroke recovery biomarkers, including neuroimaging and neurophysiological, genetic-molecular and clinical scales.

Novel Advances to Post-Stroke Aphasia Pharmacology and Rehabilitation.

Aphasia is one of the most common clinical features of functional impairment after a stroke. Approximately 21-40% of stroke patients sustain permanent aphasia, which progressively worsens one's quality of life and rehabilitation outcomes. Post-stroke aphasia treatment strategies include speech language therapies, cognitive neurorehabilitation, telerehabilitation, computer-based management, experimental pharmacotherapy, and physical medicine. This review focuses on current evidence of the effectiveness of impairment-based aphasia therapies and communication-based therapies (as well as the timing and optimal treatment intensities for these interventions). Moreover, we present specific interventions, such as constraint-induced aphasia therapy (CIAT) and melodic intonation therapy (MIT). Accumulated data suggest that using transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) is safe and can be used to modulate cortical excitability. Therefore, we review clinical studies that present TMS and tDCS as (possible) promising therapies in speech and language recovery, stimulating neuroplasticity. Several drugs have been used in aphasia pharmacotherapy, but evidence from clinical studies suggest that only nootropic agents, donepezil and memantine, may improve the prognosis of aphasia. This article is an overview on the current state of knowledge related to post-stroke aphasia pharmacology, rehabilitation, and future trends.

Biomarkers of Angiogenesis and Neuroplasticity as Promising Clinical Tools for Stroke Recovery Evaluation.

Several key issues impact the clinical practice of stroke rehabilitation including a patient's medical history, stroke experience, the potential for recovery, and the selection of the most effective type of therapy. Until clinicians have answers to these concerns, the treatment and rehabilitation are rather intuitive, with standard procedures carried out based on subjective estimations using clinical scales. Therefore, there is a need to find biomarkers that could predict brain recovery potential in stroke patients. This review aims to present the current state-of-the-art stroke recovery biomarkers that could be used in clinical practice. The revision of biochemical biomarkers has been developed based on stroke recovery processes: angiogenesis and neuroplasticity. This paper provides an overview of the biomarkers that are considered to be ready-to-use in clinical practice and others, considered as future tools. Furthermore, this review shows the utility of biomarkers in the development of the concept of personalized medicine. Enhancing brain neuroplasticity and rehabilitation facilitation are crucial concerns not only after stroke, but in all central nervous system diseases.

New Strategies for Rehabilitation and Pharmacological Treatment of Fatigue Syndrome in Multiple Sclerosis.

Multiple sclerosis (MS) is the most common autoimmune disease of the central nervous system (CNS), with an inflammatory demyelinating basis and a progressive course. The course of the disease is very diverse and unpredictable. Patients face many problems on a daily basis, such as problems with vision; sensory, balance, and gait disturbances; pain; muscle weakness; spasticity; tremor; urinary and fecal disorders; depression; and rapidly growing fatigue, which significantly influences quality of life among MS patients. Excessive fatigue occurs in most MS patients in all stages of this disease and is named MS-related fatigue. The crucial issue is the lack of effective treatment; therefore, this review focuses not only on the most common treatment methods, but also on additional novel therapies such as whole-body cryotherapy (WBC), functional electrical stimulation (FES), and non-invasive brain stimulation (NIBS). We also highlight the advantages and disadvantages of the most popular clinical scales used to measure fatigue. The entire understanding of the origins of MS-related fatigue may lead to the development of more effective strategies that can improve quality of life among MS patients. A literature search was performed using MEDLINE, EMBASE, and PEDro databases.