Neuroprotection in Acute Ischemic Stroke: A Battle Against the Biology of Nature

 Neuroprotection means nothing to a layperson. If you used the proper term,

neuronal cascade of death, maybe our researchers and doctors might have a little more alacrity in solving it. Telling your patients neuroprotection doesn't exist yet  gets a much different response from your patients than telling them, 'We are unable to stop the neuronal cascade of death which means millions, if not billions of neurons will die.'

'Reperfusion worked, but we have nothing after that, that will help you recover.'

Neuroprotection in Acute Ischemic Stroke: A Battle Against the Biology of Nature

 

Sherief Ghozy^1,2†‡, Abdullah Reda^3†‡, Joseph Varney^4†‡, Ahmed Sallam Elhawary^5‡, Jaffer Shah^6*, Kimberly Murry^7†, Mohamed Gomaa Sobeeh^8,9†, Sandeep S. Nayak¹⁰, Ahmed Y. Azzam¹¹, Waleed Brinjikji¹², Ramanathan Kadirvel¹ and David F. Kallmes¹

• ¹Department of Neuroradiology, Mayo Clinic, Rochester, MN, United States
• ²Nuffield Department of Primary Care Health Sciences and Department for Continuing Education (EBHC Program), Oxford University, Oxford, United Kingdom
• ³Faculty of Medicine, Al-Azhar University, Cairo, Egypt
• ⁴School of Medicine, American University of the Caribbean, Philipsburg, Sint Maarten
• ⁵Qena Faculty of Medicine, South Valley University, Qena, Egypt
• ⁶Medical Research Center, Kateb University, Kabul, Afghanistan
• ⁷Barry University, Miami, FL, United States
• ⁸Faculty of Physical Therapy, Sinai University, Cairo, Egypt
• ⁹Faculty of Physical Therapy, Cairo University, Giza, Egypt
• ¹⁰Department of Internal Medicine, NYC Health + Hospitals/Metropolitan, New York, NY, United States
• ¹¹Faculty of Medicine, October 6 University, Giza, Egypt
• ¹²Department of Neurosurgery, Mayo Clinic Rochester, Rochester, MN, United States

Stroke is the second most common cause of global death following coronary artery disease. Time is crucial in managing stroke to reduce the rapidly progressing insult of the ischemic penumbra and the serious neurologic deficits that might follow it. Strokes are mainly either hemorrhagic or ischemic, with ischemic being the most common of all types of strokes. Thrombolytic therapy with recombinant tissue plasminogen activator and endovascular thrombectomy are the main types of management of acute ischemic stroke (AIS). In addition, there is a vital need for neuroprotection in the setting of AIS. Neuroprotective agents are important to investigate as they may reduce mortality, lessen disability, and improve quality of life after AIS. In our review, we will discuss the main types of management and the different modalities of neuroprotection, their mechanisms of action, and evidence of their effectiveness after ischemic stroke.

Introduction

The rapid development of neurologically related deficits is a potent indicator of acute ischemic stroke (AIS) (1). This happens as a result of the presence of an acute vascular etiology that lasts for at least 24 h and focally affects the central nervous system, inducing major disturbances to the related functions of the affected areas that may even end with mortality (1, 2). In general, stroke is the second most common cause of global death following coronary artery disease, and estimates show an annual incidence of 12.2 million (3). In addition, estimates show that it affects nearly 795,000 patients in the US (4). Reports also showed that stroke is the third most common contributor to disability and increased morbidities in approximately half of the stroke survivors over 65 years of age (4, 5).

Time is crucial in managing stroke to reduce the rapidly progressing insult of the ischemic penumbra and the severe neurologic deficits that might follow (6, 7). Hence, early management provides a window of opportunity for protecting against the development of severe complications and death, subsequently enhancing the prognosis (8). Furthermore, evidence concerning the management of stroke is changing quickly. Many studies are being published that report novel technical modalities and discoveries that can help improve the outcomes of stroke (9, 10). AIS has many management routes, including intravenous (IV) thrombolytic drugs such as recombinant tissue plasminogen activator (rtPA), control of body temperature and blood sugar, and blood pressure reduction of intracranial tension and neuroprotective agents (11). While IV thrombolytic agents help restore blood flow through an occluded vessel, neuroprotective agents are very important for maintaining the function of neurons surrounding dead brain tissue and, hence, limit after-stroke deficits (12).

There is rising interest in knowing more about neuroprotective agents, as shown in the currently ongoing studies listed in Table 1. These studies aim to investigate neuroprotective agents that can be beneficial to intervene against ischemic stroke and are the intended primary outcomes of these studies. In addition, data about neuroprotection approaches can now be easily accessed through multiple national and international registries that can help researchers globally(Really? Where the fuck are they located?) However, there is still no consensus about the unified management modalities to achieve the best prognosis. Currently, the US Food and Drug Administration (FDA) has not approved a specific treatment modality as neuroprotective therapy for ischemic stroke. This study aims to elaborate on the current gold standard management modalities of AIS. We will also discuss the latest reported evidence about the neuroprotective modalities as per evidence from studies in the literature.

TABLE 1

Table 1. List of most prominent ongoing clinical trials.