Effects of Cranioplasty on Contralateral Subdural Effusion After Decompressive Craniectomy: A Literature Review.

BACKGROUND: Contralateral subdural effusion (CSE) after decompressive craniectomy (CSEDC) is occasionally observed. Cranioplasty is routinely performed for reconstruction and has recently been associated with improving contralateral subdural effusion. We sought to systematically review all available literature and evaluate the effectiveness of cranioplasty for CSE. METHODS: A PubMed, Web of Science, and Google Scholar search was conducted for preferred reporting items following the guidelines of systematic review and meta-analysis, including studies reporting patients who underwent cranioplasty because of CSEDC. RESULTS: The search yielded 8 articles. A total of 56 patients ranging in age from 21 to 71 years developed CSEDC. Of them, 32 patients underwent cranioplasty. Eighteen cases with symptomatic CSE underwent cranioplasty alone, 2 cases received Ommaya drainage later because of a recurrence of CDC, and 1 case underwent a ventriculoperitoneal shunt because the CSE did not resolve completely and the ventricle was dilated again. The symptoms of 14 cases lessened without recurrence after simultaneous cranioplasty and drainage or a shunt. The total success rate (CSE disappeared without recurrence) was 90.6% for patients who underwent cranioplasty; however, the total incidence of hydrocephalus was 40.1%. CONCLUSIONS: This review suggests that cranioplasty is effective for the treatment of CSEDC, particularly intractable cases, but early cranioplasty may be more effective. In addition, hydrocephalus is fairly common after cranioplasty and requires further treatment.

Effects of the Notch Signaling Pathway on Secondary Brain Changes Caused by Spinal Cord Injury in Mice.

Spinal cord injury (SCI) can cause secondary brain changes, leading to hypomyelination in the dorsolateral prefrontal cortex (dlPFC). Some studies have shown that notch signaling pathway activation can regulate oligodendrocyte maturation and myelination. The aim of this study was to investigate whether inhibition of the Notch signaling pathway can alleviate hypomyelination in the dlPFC caused by SCI. Moreover, we further investigated whether the changes in myelination in the dlPFC are associated with neuropathic pain following SCI. We established a mouse model of SCI and observed the changes in mechanical and thermal hyperalgesia. Western blotting and immunofluorescence were used to analyze the changes in myelination in the dlPFC. The results indicated the existence of a relationship between activation of the Notch signaling pathway and hypomyelination in the dlPFC and confirmed the existence of a relationship between hypomyelination in the dlPFC and decreases in mechanical and thermal hyperalgesia thresholds. In conclusion, these results suggested that the Notch signaling pathway is activated after SCI, leading to hypomyelination in the dlPFC, and that DAPT can inhibit the Notch signaling pathway and improve mechanical and thermal hyperalgesia thresholds. Our findings provide a new target for the treatment of neuropathic pain caused by SCI.

Spinal Cord Injury Inhibits the Differentiation and Maturation of NG2 Cells in the Cerebellum in Mice.

OBJECTIVE: Neuroimaging studies have shown that spinal cord injury (SCI) may lead to significant brain changes that are the key factors affecting functional recovery. However, little is known about the molecular and cellular biological mechanisms of these brain changes. The aim of this study was to investigate the molecular and cellular biological changes in the cerebellum after SCI. METHODS: A total of 72 mice were randomly divided into 2 groups: sham group and SCI group. A mouse model of SCI was established by an aneurysm clip. Pathological examinations of the injured site were performed by hematoxylin and eosin staining and immunohistochemical. Western blot and immunohistochemical were used to determine the effect of SCI on the differentiation and maturation of NG2 cells. RESULTS: Compared with the sham group, the spinal cord tissue structure was disrupted and the motor function decreased significantly in the SCI group; the number of NG2 cells in the ansiform lobule crus Ⅰ increased on the 7th and 14th days, whereas the expression of oligodendrocyte transcription factor 2, myelin basic protein, and proteolipid protein decreased on the 7th and 14th days after SCI. These results showed that the differentiation and maturation of NG2 cells in the ansiform lobule crus Ⅰ were inhibited after SCI, resulting in the decrease of the formation of mature oligodendrocytes. CONCLUSIONS: These results indicate that SCI can lead to secondary changes in the cerebellum, which may affect the functional recovery. These findings may be used as biomarkers to evaluate the secondary changes in the brain after SCI.

The Notch Signaling Pathway Regulates Differentiation of NG2 Cells into Oligodendrocytes in Demyelinating Diseases.

NG2 cells are highly proliferative glial cells that can self-renew or differentiate into oligodendrocytes, promoting remyelination. Following demyelination, the proliferative and differentiation potentials of NG2 cells increase rapidly, enhancing their differentiation into functional myelinating cells. Levels of the transcription factors Olig1 and Olig2 increase during the differentiation of NG2 cells and play important roles in the development and repair of oligodendrocytes. However, the ability to generate new oligodendrocytes is hampered by injury-related factors (e.g., myelin fragments, Wnt and Notch signaling components), leading to failed differentiation and maturation of NG2 cells into oligodendrocytes. Here, we review Notch signaling as a negative regulator of oligodendrocyte differentiation and discuss the extracellular ligands, intracellular pathways, and key transcription factors involved.

Glycyrrhizic Acid Attenuates the Inflammatory Response After Spinal Cord Injury by Inhibiting High Mobility Group Box-1 Protein Through the p38/Jun N-Terminal Kinase Signaling Pathway.

BACKGROUND: Neuroinflammation is an important secondary aggravating factor in spinal cord injury (SCI). Inhibition of the inflammatory response is critical for SCI treatment. Glycyrrhizic acid (GA) is an anti-inflammatory drug, but its utility for SCI is unclear. This study aimed to evaluate the effects of GA on inflammation after SCI and the underlying mechanism. METHODS: Cell counting kit-8 assays were performed to assess the viability of highly aggressively proliferating immortalized cells that had been treated with lipopolysaccharide (LPS) and/or GA. Reverse transcription quantitative polymerase chain reaction and Western blotting were performed to assess expression of high mobility group box-1 protein (HMGB1), ionized calcium binding adaptor molecule 1, and inflammatory factors in vitro and in vivo. GA (100 mg/kg) was intraperitoneally injected into rats. Anti-inflammatory effects of GA were analyzed in SCI tissues. p38/Jun N-terminal kinase signaling pathway proteins were analyzed by Western blotting. RESULTS: Cell counting kit-8 assay results showed that treatment with 100 ng/mL LPS for 12 hours was optimal. After LPS treatment, highly aggressively proliferating immortalized cells were activated; messenger RNA expression levels of HMGB1 and inflammatory factors were increased. GA significantly inhibited LPS-induced HMGB1 expression and inflammatory responses, as determined by reverse transcription quantitative polymerase chain reaction and Western blotting. Transfection with an HMGB1-overexpression plasmid reversed the anti-inflammatory effects of GA. In addition, intraperitoneal injection of GA (100 mg/kg) into rats for 3 days significantly reduced expression levels of HMGB1 and inflammatory factors after SCI in vivo. GA reduced phosphorylation, but not levels, of p38 and Jun N-terminal kinase proteins. CONCLUSIONS: GA attenuates the inflammatory response after SCI by inhibiting HMGB1 through the p38/JNK signaling pathway and thus has therapeutic potential for SCI.

Relationship Between Serum Fibrinogen Level and Depressive Symptoms in an Adult Population with Spinal Cord Injury: A Cross-Sectional Study.

PURPOSE: Depression is associated with an inflammatory immune response. There are minimal data regarding the association of inflammatory markers with depression in patients with spinal cord injury (SCI). We aimed to investigate the association of inflammatory markers with depression in middle-aged and elderly SCI patients. METHODS: Data were obtained from the Midlife in the United States (MIDUS) study, a longitudinal study of a representative sample of the adult population. We analyzed the associations of serum levels of fibrinogen, interleukin-6, tumor necrosis factor-ɑ, and C-reactive protein with depressive symptoms. RESULTS: The median participant age was 52.5 years; 44.9% of participants were men. Multivariate linear regression analyses showed that an increased serum fibrinogen level (Sß = 0.114, p = 0.005) was associated with higher Centre for Epidemiological Studies-Depression (CES-D) scores after adjustment for age, sex, body mass index (BMI), ethnicity, education, marital status, smoking, alcohol use, exercise, perceived stress score, and cardiovascular disease (CVD). Multivariate logistic regression analysis showed that an increased serum fibrinogen level was independently associated with a history of depression (odds ratio [OR] = 1.240, 95% confidence interval [CI] = 1.103-1.997, p = 0.012) and depressive symptoms (OR = 1.884, 95% CI = 1.165-2.499, p < 0.001; CES-D score ≥ 16) after adjustment for confounding factors. Stratified analysis revealed that the association between serum fibrinogen level and depressive symptoms was affected by antidepressant use. CONCLUSION: Serum fibrinogen level had a significantly positive association with depressive symptoms in middle-aged and elderly patients with SCI. Future longitudinal cohort studies should evaluate the possible use of serum fibrinogen for diagnosis of depression in SCI patients.

Potential Correlation Between Depression-like Behavior and the Mitogen-Activated Protein Kinase Pathway in the Rat Hippocampus Following Spinal Cord Injury.

BACKGROUND: Depression induced by spinal cord injury (SCI) has been demonstrated in clinical and experimental studies; it significantly impacts patients' lives and may be associated with changes in the hippocampus. However, the biological mechanisms underlying depression after SCI are unknown. The mitogen-activated protein kinase (MAPK) signaling pathway participates in potential mechanisms of depression; it is unknown whether this pathway plays a role in SCI-induced depression. METHODS: We applied an animal model of depression induced by SCI, established using an aneurysm clip, to determine whether MAPK activation in the hippocampus is associated with depression-like behavior. RESULTS: SCI led to depression-like behavior, such as anhedonia in the sucrose preference test, decreased number of crossings in the open field test, decreased body weight, and decreased immobility time in the forced swim test. Western blot analysis further showed that SCI significantly increased the levels of phosphorylated p38 MAPK and cleaved caspase-3 in the hippocampus and inhibited the phosphorylation of extracellular signal-related kinase 1/2 and c-Jun N-terminal kinase 1/2. In addition, there were significant negative correlations between depression-like behavior and phosphorylated extracellular signal-related kinase 1/2 and positive correlations between depression-like behavior and phosphorylated p38 MAPK and cleaved caspase-3. CONCLUSIONS: These findings suggest that the MAPK pathway in the rat hippocampus may be involved in the pathophysiology of depression induced by SCI.

Driving effect of BDNF in the spinal dorsal horn on neuropathic pain.

Neuropathic pain (NP) is caused by direct or indirect damage to the nervous system and is a common symptom of many diseases. The mechanisms underlying the onset and persistence of NP are unclear. Therefore, research concerning these mechanisms has become an important focus in the medical field. Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophic factor family of signaling molecules. BDNF is an important regulator of neuronal development, synaptic transmission, and cellular and synaptic plasticity, which are essential for nerve maintenance and repair. However, BDNF is upregulated in the spinal dorsal horn and can promote NP by activating glial cells, reducing inhibitory functions and enhancing excitement after nociceptive stimulation. This review considers the relationship between NP and BDNF signaling in the spinal dorsal horn and discusses potentially related pathological mechanisms.