Brain and disease: an insight into new developments in the pathogenesis and novel therapies for neurological disorders

Neurological diseases such as stroke, epilepsy, Alzheimer’s disease and other dementias, and migraines are the leading causes of disability worldwide [1]. This Special Issue of Neurological Research expands on the most recent understandings in pathogenesis of cerebral disorders and aims to update the reader on the latest developments in treating these conditions with hopes of discovering novel treatments that can significantly improve outcomes. In an effort to improve our understanding of cerebral disorders, we have selected a total of 14 representative papers comprising of clinical and basic science studies that will provide the reader a wide spectrum of recent developments in the field. Our focus is on improving outcomes and preventing neurological disability and we hope that this issue will address this area of research.

This issue begins with a mini review by Zhu et al. that discusses recent research on garlic extract and its potential in treating vascular diseases. Garlic (Allium sativum) has been identified as a therapeutic by many different cultures over hundreds of years. Moreover, in the last few decades, scientific research has explored the use of garlic extract to treat cancer, hypertension and diabetes among other diseases. Zhu’s group discusses various mechanisms how garlic extract can treat vascular diseases and how this can translate to treating cerebrovascular disorders in clinical practice.

Post-stroke epileptic (PSE) seizures are a common occurrence in elderly stroke patients and account for almost half of all newly diagnosed epilepsy cases in this patient population. Moreover, PSE has been associated with more frequent hospital readmission, poorer quality of life and increased rates of mortality in stroke patients between the ages of 18 and 50 years [2,3]. Wang’s group aims to elaborate the pathogenesis of PSE and discuss therapies to control and possibly treat PSE, sharing with the reader the current methods of management of PSE and candidate therapies. Moreover, while not related directly to stroke, Zhang et al. explore the utility of using cortico-cortical evoked potentials as a novel diagnostic strategy for detecting seizure onset zones in refractory epilepsy patients, the utility of which should be explored in the use for stroke-related epilepsy.

Ever since its introduction in 1996, thrombolysis with intravenous tissue-type plasminogen activator (tPA) remains the only FDA approved treatment for acute ischemic stroke in spite of its narrow therapeutic window. Thus, in order to find more effective and safer therapies, many groups have been investigating potential candidates to fill in this large gap. In this issue, two articles reveal potential adjuvant and preventative therapies for acute stroke. In a systematic review and meta-analysis by Ding et al., the authors elucidate the effects of normobaric oxygen therapy for patients in an acute stroke setting. In exploring this controversial topic, the authors reveal NBO to be a beneficial therapy in acute stroke due to several mechanisms, which also extends the therapeutic window for tPA use. Along the same lines, Shen et al. demonstrate the use of Omega-3 fatty acid supplementation to slow down intracranial atherosclerosis thereby reducing the risk of ischemic stroke. Both these studies highlight the importance of newer therapies that can be used in the clinic and supplements that can reduce the risk of ischemic stroke, respectively.

Another highlight of this issue is understanding the risk factors for intracerebral hemorrhage (ICH). Of all types of strokes, ICH occurs from 10–15% in the West to 20–30% in the Eastern world largely due to several diverse biological and social risk factors [4]. Sadly, almost half of those affected by ICH die within a month of the event and only a fifth of all ICH patients have good outcomes [5,6]. In this issue Yan et al. predictive factors for mortality and recurrence of ICH in affected patients, respectively [5]. Findings this study studies will help the clinicians identify the most clinically vulnerable patients and provide them timely and appropriate clinical care.

Intracranial aneurysms are a common occurrence with up to 5–10% of the general population being affected [7,8]. These aneurysms are characterized by focal structural deterioration of the internal elastic lamina and disruption of the media of the arterial wall. Due to the loss of integrity of the arterial wall, the most feared complication is rupturing of these structures. Endovascular coil embolization using various stent systems is a safe and wide used treatment for aneurysms. In a prospective study by Yang’s group, the authors assessed the efficacy of a next generation Low-profile Visualized Intraluminal Support (LVIS) stent and found these stents to have higher complete occlusion rate of aneurysms with very low complications. Such findings are encouraging in using next generation stents more widely as well as developing newer stenting devices that have a higher rate of efficacy than the current gold standard.

In addition to the studies mentioned above, this issue covers other interesting and important clinical reports related to cerebrovascular diseases such as those assessing risk factors and prognosis of dolichoectasia in non-cardioembolic transient ischemic attack and minor stroke, effects of varying frequencies of repetitive transcranial magnetic stimulation in stroke patients with non-fluent aphasia, and assessing the efficacy of neuromuscular electrical stimulation in improving the negative psychological state in patients with cerebral infarction and dysphagia. On the other hand, this special issue also expands on a few but important non-stroke-related reports to capture a broader spectrum of neurological and cerebral diseases. Chen et al. reveal that in early stages of Parkinson’s disease, postural sway along with deficits in stereopsis is a common finding in a subset of patients, while Zhang et al. explore the effects of pretreatment with Trimetazidine, an anti-angina drug, on psycho-cardiac disease.

We wrap up this special issue with a basic science study that elucidates an underlying mechanism of neuroprotection induced by hypothermia in ischemic stroke. The authors of this study, led by Liu, reveal that focal hypothermia therapy following ischemic stroke reduced brain tissue loss four weeks after the stroke event. This is explained by preferential microglial polarization to an anti-inflammatory ‘M2’ phenotype over the M1 ‘detrimental’ or ‘ill’ phenotype as detected by the authors at the transcriptional level suggesting that tissue protection is driven by microglial expression of anti-inflammatory genes.

This special issue would not have been a reality if it was not for the hard work of the authors who have contributed to the journal. We applaud them and thank them for their contributions. Moreover, a special thank you must be given to Professor Ben Roitberg, the Editor-in-Chief of this journal, for his continual support and without whom this special issue would not have been a possibility. We hope this special issue contributes to the advancement of the field of neurology and neurosurgery, and we encourage the scientific community to continue to add to the current ongoing discussion in neurological disorders of the brain.

Ankush Chandra
Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, USA
Department of Neurological Surgery, University of California, San Francisco (UCSF), CA, USA
http://orcid.org/0000-0003-1843-3894
Xiaokun Geng
Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, USA
Department of Neurology, Beijing Luhe Hospital, Capital Medical University, China
Yuchuan Ding
Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, USA
Department of Neurology, Beijing Luhe Hospital, Capital Medical University, China
[email protected], [email protected]