Open Access Original Research Issue
Lithium ameliorates spinal cord injury through endoplasmic reticulum stress-regulated autophagy and alleviated apoptosis through IRE1 and PERK/eIF2α signaling pathways
Journal of Neurorestoratology 2023, 11 (4): 100081
Published: 12 October 2023

This study aims to investigate the role of apoptosis and autophagy under endoplasmic reticulum (ER) stress in a lithium-treated SCI model.


We established a rat thoracic 10 (T10) spinal cord contusion model and observed its therapeutic effect by intraperitoneal (IP) injection of lithium. Histological and behavioral recovery with or without lithium injection were evaluated after rat spinal cord injury. In addition, we employed an oxygen-glucose deprivation (OGD)-PC12 cell model to study the effects of lithium on OGD-PC12 cell apoptosis, autophagy and ER stress.


We found that lithium administration to SCI rats reduced neuronal apoptosis and autophagy, restored rat locomotor function by reducing ER stress via IRE1 and PERK/eIF2α pathways. In vitro experiments confirmed that upon lithium treatment, OGD-PC12 cells resisted ER stress caused by thapsigargin (TG) via the IRE1 and PERK/eIF2α signaling pathways.


Lithium attenuated neuronal apoptosis and autophagy, and facilitates the recovery after spinal cord injury through ameliorating ER stress, providing a new therapeutic mechanism for lithium to treat SCI.

Open Access Review Article Issue
Advances and prospects of cell therapy for spinal cord injury patients
Journal of Neurorestoratology 2022, 10 (1): 13-30
Published: 05 March 2022

Spinal cord injury (SCI) is catastrophic damage for patients, their family, and society. Researchers and clinicians have been trying to find neurorestorative methods to recover their injured functions and structures. Cell therapy is one of the effective therapeutic strategies for SCI. And it can partially restore their neurological functions, which are once thought as permanent neurological deficits. Currently, cells being used therapeutically in clinic include olfactory ensheathing cells (OECs), mononuclear cells (MNCs), mesenchymal stromal cells (MSCs), Schwann cells, and hematopoietic stem cells, cell products differentiated from embryonic stem cells, mesenchymal stem cells, induced pluripotent stem cells, and neural stem cells as well as other kinds of cells. Real world data from these cell therapies showed some benefits in some patients with SCI. Due to being affected by many factors, the therapeutic results of some kinds of cells are contradictory and it is hard to compare effects among different types of cells. According to the data of cell therapies, OEC, MNC and MSC transplantation are applied for patients in majority percentage of cases, and OEC transplantation had a higher percentage of benefits. In next step, under the unified standard of cell preparation and quality control as well as the guidelines of clinical cell application, each kind of cells including OECs should be studied using prospective, multicenter, double-blind or observing-blind, placebo-control, randomized studies for SCI patients with different level of injury and chronicity.

Open Access Research Article Issue
Ten years of clinical observation of olfactory ensheathing cell transplantation in patients with spinal cord injury
Journal of Neurorestoratology 2021, 9 (2): 106-116
Published: 05 June 2021

To evaluate the long-term curative efficacy and safety of olfactory ensheathing cell (OEC) transplantation by 10 years of follow-up investigation.


A follow-up observation was done on 13 patients with allograft olfactory bulb-derived OEC transplantation from September 2005 to September 2007 at the Second Affiliated Hospital of Xi’an Jiaotong University. After cell purification, amplification, and identification, a 2 × 107/mL cell suspension was prepared for transplantation. In the posterior horn of the spinal cord 0.5 cm distal and proximal to the spinal cord injury zone, 4 needle points were selected to avoid the blood vessels. The needle depth was 3 mm, and the injection volume per point was 10 μL. Postoperatively and at 1 week, 4 weeks, 12 weeks, 24 weeks, 1 year, 3 years, 5 years, and 10 years after the surgery, the patient’s American Spinal Injury Association (ASIA) score, adverse reactions, and other minor observations were assessed.


All the patients did not have serious complications. No gliomas or other new organisms formed during the 10-year observation period. Eight of 13 patients had improvement in sensory function, and 5 patients showed improvement in motor function. The ASIA acupuncture, light touch, and exercise scores improved significantly 1 year after the surgery, and this improvement continued until the 10-year follow-up period. Three of 13 patients had improvement in defecation and urination, and 1 patient had improved neuralgia after spinal cord injury.


OEC transplantation is safe and effective in treating spinal cord injury. The observation period of OEC transplantation is 1 to 3 years.

Open Access Review Article Issue
Muse cells and Neurorestoratology
Journal of Neurorestoratology 2019, 7 (1): 18-25
Published: 22 March 2019

Multilineage-differentiating stress-enduring (Muse) cells were discovered in 2010 as a subpopulation of mesenchymal stroma cells (MSCs). Muse cells can self-renew and tolerate severe culturing conditions. These cells can differentiate into three lineage cells spontaneously or in induced medium but do not form teratoma in vitro or in vivo. Central nervous system (CNS) diseases, such as intracerebral hemorrhage (ICH), cerebral infarction, and spinal cord injury are normally disastrous. Despite numerous therapy strategies, CNS diseases are difficult to recover. As a novel kind of pluripotent stem cells, Muse cells have shown great regeneration capacity in many animal models, including acute myocardial infarction, hepatectomy, and acute cerebral ischemia (ACI). After injection into injury sites, Muse cells survived, migrated, and differentiated into functional neurons with synaptic junctions to local neurons and contributed to recovery of function. Furthermore, Muse cell differentiation did not need to be induced pre-transplantation and no tumors were observed post- transplantation. The Muse cell population is promising and may lead to a revolution in regenerative medicine. This review focuses on recent advances regarding the Muse cells therapies in Neurorestoratology and discusses future perspectives in this field.

Open Access Expert Opinion Issue
Clinical therapeutic guideline for neurorestoration in spinal cord injury (Chinese version 2016)
Journal of Neurorestoratology 2017, 5 (1): 73-83
Published: 03 April 2017

Restoring functions following spinal cord injury (SCI) was the most challenging task in clinical practice in the past. Fortunately, some effective neurorestorative methods have been exploited in acute, subacute, and chronic phase of SCI. There were no clinical neurorestorative therapeutic guidelines available before this document which can be followed by physicians to manage patients with acute, subacute, and chronic SCI. This guideline will be a helpful reference to physicians to implement their neurorestorative strategies that can help to improve the neurological functions in patients with SCI and their quality of life.

Open Access Review Issue
Anti-inflammatory effect of stem cells against spinal cord injury via regulating macrophage polarization
Journal of Neurorestoratology 2017, 5 (1): 31-38
Published: 13 February 2017

Spinal cord injury (SCI) is a traumatic event that involves not just an acute physical injury but also inflammation-driven secondary injury. Macrophages play a very important role in secondary injury. The effects of macrophages on tissue damage and repair after SCI are related to macrophage polarization. Stem cell transplantation has been studied as a promising treatment for SCI. Recently, increasing evidence shows that stem cells, including mesenchymal stem, neural stem/progenitor, and embryonic stem cells, have an anti-inflammatory capacity and promote functional recovery after SCI by inducing macrophages M1/M2 phenotype transformation. In this review, we will discuss the role of stem cells on macrophage polarization and its role in stem cell-based therapies for SCI.

Open Access Expert Opinion Issue
Clinical cell therapy guidelines for neurorestoration (China version 2016)
Journal of Neurorestoratology 2017, 5 (1): 39-46
Published: 13 February 2017

Cell therapy has been shown to be a key clinical therapeutic option for central nervous system disease or damage, and >30 types of cells have been identified through preclinical studies as having the capacity for neurorestoration. To standardize the clinical procedures of cell therapy as one of the strategies for treating neurological disorders, the first set of guidelines governing the clinical application of neurorestoration was completed in 2011 by the Chinese Branch of the International Association of Neurorestoratology. Given the rapidly advancing state of the field, the Neurorestoratology Professional Committee of Chinese Medical Doctor Association (Chinese Association of Neurorestoratology) and the Chinese Branch of the International Association of Neurorestoratology have approved the current version known as the "Clinical Cell Therapy Guidelines for Neurorestoration (China Version 2016)". We hope this guideline will reflect the most recent results demonstrated in preclinical research, transnational studies, and evidence-based clinical studies, as well as guide clinical practice in applying cell therapy for neurorestoration.

total 7