Correlation of Circulating T Lymphocytes and Intracranial Hypertension in Intracerebral Hemorrhage.

BACKGROUND: The close correlation between intracerebral pressure (ICP) and immunologic responses has been well described, but the role of T lymphocytes in this process remains unknown. This study targeted the relationship of circulating T lymphocytes and ICP in patients with intracerebral hemorrhage (ICH). METHODS: Between October 2015 and October 2016, consecutive patients age 18-65 years with ICH were enrolled. ICP values were recorded hourly for 5 days, and the screened patients were divided into 2 groups based on ICP: the elevated ICP group (ICP >20 mmHg) and normal ICP group (ICP ≤20 mmHg). Peripheral blood was collected on admission and T lymphocyte subpopulations were analyzed by flow cytometry. Glasgow Coma Scale score on admission and Glasgow Outcome Scale (GOS) score at 30 days after ICH were analyzed. RESULTS: A total of 44 patients were enrolled, including 18 patients in the elevated ICP group and 26 in the normal ICP group. Both CD3+ and CD4+ T lymphocyte counts were higher in the elevated ICP group (P = 0.004 and 0.000, respectively). The CD8+ T lymphocyte count was not significantly different between the 2 groups (P = 0.751). There were correlation trends between the maximum ICP value and CD3+ lymphocyte count (P = 0.003), CD4+ T lymphocyte count (P = 0.000), and the CD4+/CD8+ T lymphocyte ratio (P = 0.000). The area under the curve (AUC) of CD4+/CD8+ T lymphocyte ratio was the largest among them (P = 0.011 and 0.033), with a significant cutoff value and good specificity and sensitivity. There was a close correlation between the CD4+/CD8+ T lymphocyte ratio and the 30-day GOS score (P = 0.003, AUC = 0.812). CONCLUSIONS: The CD4+/CD8+ T lymphocyte ratio may be a valuable indicator for predicting postoperative ICP and the short-term prognosis after ICH.

A Three-Day Consecutive Fingolimod Administration Improves Neurological Functions and Modulates Multiple Immune Responses of CCI Mice.

Excessive inflammation after traumatic brain injury (TBI) is a major cause of secondary TBI. Though several inflammatory biomarkers have been postulated as the risk factors of TBI, there has not been any comprehensive description of them. Fingolimod, a new kind of immunomodulatory agent which can diminish various kinds of inflammatory responses, has shown additional therapeutic effects in the treatment of intracranial cerebral hematoma (ICH), ischemia, spinal cord injury (SCI), and many other CNS disorders. However, its therapeutic application has not been confirmed in TBI. Thus, we hypothesized that a 3-day consecutive fingolimod administration could broadly modulate the inflammatory reactions and improve the outcomes of TBI. The TBI models of C57/BL6 mice were established with the controlled cortical impact injury (CCI) system. A 3-day consecutive fingolimod therapy (given at 1, 24, and 48 h post injury) was performed at a dose of 1 mg/kg. The flow cytometry, immunoflourence, cytokine array, and ELISA were all applied to evaluate the immune cells and inflammatory markers in the injured brains. Immunohistochemical staining with anti-APP antibody was performed to assess the axonal damage. The neurological functions of these TBI models were assessed by mNSS/Rota-rod and Morris water maze (MWM). The brain water content and integrity of the blood-brain barrier (BBB) were also observed. On the 3rd day after TBI, the accumulation of inflammatory cytokines and chemokines reached the peak and administration of fingolimod reduced as many as 20 kinds of cytokines and chemokines. Fingolimod decreased infiltrated T lymphocytes and NK cells but increased the percentage of regulatory T (Treg) cells, and the concentration of IL-10 on the 3rd day after TBI. Fingolimod also notably attenuated the general activated microglia but augmented the M2/M1 ratio accompanied by decreased axonal damage. The neurological functions were improved after the fingolimod treatment accompanied with alleviation of the brain edema and BBB damage. This study suggests that the 3-day consecutive fingolimod administration extensively modulates multiple immuno-inflammatory responses and improves the neurological deficits after TBI, and therefore, it may be a new approach to the treatment of secondary TBI.