Intravenous tPA therapy does not worsen acute intracerebral hemorrhage in mice

Tissue plasminogen activator (tPA) is the only FDA-approved treatment for reperfusing ischemic strokes. But widespread use of tPA is still limited by fears of inadvertently administering tPA in patients with intracerebral hemorrhage (ICH). Surprisingly, however, the assumption that tPA will worsen ICH has never been biologically tested. Here, we assessed the effects of tPA in two models of ICH. In a mouse model of collagenase-induced ICH, hemorrhage volumes and neurological deficits after 24 hrs were similar in saline controls and tPA-treated mice, whereas heparin-treated mice had 3-fold larger hematomas. In a model of laser-induced vessel rupture, tPA also did not worsen hemorrhage volumes, while heparin did. tPA is known to worsen neurovascular injury by amplifying matrix metalloproteinases during cerebral ischemia. In contrast, tPA did not upregulate matrix metalloproteinases in our mouse ICH models. In summary, our experimental data do not support the assumption that intravenous tPA has a deleterious effect in acute ICH. However, due to potential species differences and the inability of models to fully capture the dynamics of human ICH, caution is warranted when considering the implications of these findings for human therapy

N-3 Polyunsaturated Fatty Acids and the Resolution of Neuroinflammation

In the past few decades, as a result of their anti-inflammatory properties, n-3 long chain polyunsaturated fatty acids (n-3 LC-PUFAs), have gained greater importance in the regulation of inflammation, especially in the central nervous system (in this case known as neuroinflammation). If sustained, neuroinflammation is a common denominator of neurological disorders, including Alzheimer's disease and major depression, and of aging. Hence, limiting neuroinflammation is a real strategy for neuroinflammatory disease therapy and treatment. Recent data show that n-3 LC-PUFAs exert anti-inflammatory properties in part through the synthesis of specialized pro-resolving mediators (SPMs) such as resolvins, maresins and protectins. These SPMs are crucially involved in the resolution of inflammation. They could be good candidates to resolve brain inflammation and to contribute to neuroprotective functions and could lead to novel therapeutics for brain inflammatory diseases. This review presents an overview 1) of brain n-3 LC-PUFAs as precursors of SPMs with an emphasis on the effect of n-3 PUFAs on neuroinflammation, 2) of the formation and action of SPMs in the brain and their biological roles, and the possible regulation of their synthesis by environmental factors such as inflammation and nutrition and, in particular, PUFA consumption

Incidence of symptomatic adjacent vertebral fractures after percutaneous balloon kyphoplasty in osteoporotic vertebral fractures

To investigate the long-term outcome of 203 patients with osteoporotic vertebra fractures who were treated with percutaneous kyphoplasty (PKP) technique under local anesthesia. Magnetic resonance and Computed Tomography Image results were used and correlated with clinical presentations to identify the symptomatic vertebral acute fracture levels. Percutaneous kyphoplasty was performed under local anesthesia/sedation technique in these patients. During the follow-up, pain symptoms were recorded on a self-reported visual analog scale (VAS). 203 patients (78 males and 125 females) with traumatic osteoporotic vertebral fractures in our clinic between 2015 and 2020. Patients VAS scores significantly decreased from 8.48±1.1 to 3.30±1.89 after 10 days of treatment (p [Med-Science 2022; 11(1.000): 321-5

Treatment with FTY720 has no beneficial effects on short-term outcome in an experimental model of intracerebral hemorrhage

Background: No evidence-based therapy is available for patients with acute intracerebral hemorrhage (ICH). In view of the profound inflammatory reaction in the perilesional tissue, we investigated in a well-characterized experimental model whether the administration of the immunomodulator fingolimod (FTY720) is neuroprotective in acute ICH. Methods: ICH was induced by means of a stereotactic intrastriatal injection of collagenase type VII-S. FTY720 (1 mg/kg) was administered intraperitoneally 1 h after ICH induction. Hematoma volume was assessed spectrophotometrically at 24 h after ICH induction. The following endpoints were determined at 24 and 72 h, respectively: mortality rate and neurologic outcomes, edema formation, and MMP-9 activity. Results: Twenty-four hour after ICH induction, hematoma volume was not statistically different between groups. No difference was found in mortality and neurologic outcomes at 24 and 72 h between FTY720 treated mice and controls. Edema formation was present in both groups on the ipsilateral side with no statistical difference between groups at both time points. No difference was found in MMP-9 levels after 24 and 72 h between groups. Conclusions: Our results suggest that FTY720 has no beneficial effects in the acute phase of experimental ICH. Electronic supplementary material The online version of this article (doi:10.1186/s13231-016-0016-z) contains supplementary material, which is available to authorized users

Contributions of 12/15-Lipoxygenase to Bleeding in the Brain Following Ischemic Stroke.

Ischemic strokes are caused by one or more blood clots that typically obstruct one of the major arteries in the brain, but frequently also result in leakage of the blood-brain barrier and subsequent hemorrhage. While it has long been known that the enzyme 12/15-lipoxygenase (12/15-LOX) is up-regulated following ischemic strokes and contributes to neuronal cell death, recent research has shown an additional major role for 12/15-LOX in causing this hemorrhagic transformation. These findings have important implications for the use of 12/15-LOX inhibitors in the treatment of stroke

Burden of Vaccine-Preventable Diseases in People Living with HIV

Vaccine-preventable diseases (VPDs) pose a serious public health concern for people living with HIV (PLH). PLH experience a delayed and weakened response to many vaccines available, compared to the general population. Lower seroconversion rates, along with a decreased efficacy and durability of vaccines, increases the susceptibility of PLH to VPDs. Vaccination guidelines specifically targeting this population have been modified to overcome these challenges. However, vaccine uptake remains suboptimal due to multiple barriers, highlighting the need for further studies and the additional implementation of public health measures specifically tailored to PLH