What's known on the subject? and What does the study add? A single set of botulinum toxin A (BoNT‐A) injections relieves clinical symptoms of interstitial cystitis/bladder pain syndrome (IC/BPS), but lacks long‐term effect. An inadequate anti‐inflammatory effect is likely to cause treatment failure. The study shows that chronic inflammation and apoptotic signalling molecules are significantly reduced after repeated intravesical BoNT‐A injection in patients with IC/BPS. It also shows that repeated BoNT‐A injections are necessary to achieve greater success in the treatment of IC/BPS. Objective To investigate the mechanisms of action of botulinum toxin A (BoNT‐A) treatment on interstitial cystitis/bladder pain syndrome (IC/BPS). Patients and Methods A total of 23 women with IC/BPS who received single intravesical BoNT‐A injection were studied. Among them, 11 received three repeated injections every 6 months to improve their symptoms. Bladder biopsy was obtained before each BoNT‐A injection and the clinical symptoms and urodynamic variables were recorded. Immunohistochemical (IHC) staining for TUNEL and mast cell activity, and western blotting analysis of tryptase, cytokines, Bax and phospho‐p38 (p‐p38) were carried out. We compared the clinical results and IHC data among baseline, single or repeated BoNT‐A treatments. Results Single BoNT‐A injection improved clinical symptoms, pain score and daytime urinary frequency. Mast cell activity and apoptotic cell count did not decrease significantly, while Bax and p‐p38, but not tryptase, decreased significantly after a single BoNT‐A injection. The 11 patients who received three repeated BoNT‐A injections had significantly lower pain scores than the remaining patients (mean [SD]: 5.80 [2.27] vs. 3.03 [2.30], P = 0), glomerulation degree (mean [SD]: 1.80 [1.06] vs. 1.20 [1.06], P = 0.026) and global response scores (mean [SD]: 0.30 [0.92] vs. 1.20 [1.06], P = 0) after treatment. Tryptase, Bax, p‐p38 and apoptotic cell counts all decreased significantly. 25‐kD synaptosomal‐associated protein also decreased after BoNT‐A treatments, which confirmed the therapeutic effect of repeated BoNT‐A injections. Conclusions Chronic inflammation and apoptotic signalling molecules were significantly reduced after repeated BoNT‐A injections in patients with IC/BPS. The IHC improvement was associated with clinical symptom improvement. Repeated BoNT‐A injections are necessary to achieve a greater success rate in the treatment of IC/BPS.

Intracerebral hemorrhage (ICH) is a major cause of stroke, with high mortality and morbidity. There is no effective pharmacological therapy for ICH. Previous studies have indicated that CXCR4 antagonists reduced microglia activation, attenuated infiltration of T cells, and improved functional recovery in ischemic stroke animals. The interaction of CXCR4 antagonists and ICH has not been characterized. The purpose of this study is to examine the neuroprotective action of a novel CXCR4 antagonist CX807 against ICH. In primary cortical neuronal and BV2 microglia co-culture, CX807 reduced glutamate-mediated neuronal loss and microglia activation. Adult rats were locally administered with collagenase VII to induce ICH. CX807 was given systemically after the ICH. Early post-treatment with CX807 improved locomotor activity in ICH rats. Brain tissues were collected for qRTPCR and histological staining. ICH upregulated the expression of CXCR4, CD8, TNFα, IL6, and TLR4. The immunoreactivity of IBA1 and CD8, as well as TUNEL labeling, were enhanced in the perilesioned area. CX807 significantly mitigated these responses. In conclusion, our data suggest that CX807 is neuroprotective and anti-inflammatory against ICH. CX807 may have clinical implications for the treatment of hemorrhagic stroke.

Background: Accumulation of ␣-synuclein (␣Syn) in the dopaminergic neurons is a common pathology seen in patients with Parkinson's disease (PD). Overproduction of ␣Syn potentiates the formation of oligomeric ␣Syn aggregates and enhances dopaminergic neuron degeneration. Downregulating intracellular monomeric ␣Syn prevents the formation of ␣Syn oligomers and is a potential therapeutic strategy to attenuate the progression of PD. Objective: The purpose of this study is to investigate the efficacy of gene delivery of ␣Syn-specific single-chain antibodies in vitro and in vivo. Methods and Results:The plasmids for ␣Syn and selective antibodies (NAC32, D10, and VH14) were constructed and were transfected to HEK293 and SH-SY5Y cells. Co-expression of ␣Syn with NAC32, but not D10 or VH14, profoundly downregulated ␣Syn protein, but not ␣Syn mRNA levels in these cells. The interaction of ␣Syn and NAC32 antibody was next examined in vivo. Adeno-associated virus (AAV)-␣Syn combined with AAV-NAC32 or AAV-sc6H4 (a negative control virus) were stereotactically injected into the substantia nigra of adult rats. AAV-NAC32 significantly reduced AAV-encoded ␣Syn levels in the substantia nigra and striatum and increased tyrosine hydroxylase immunoreactivity in the striatum. Also, in the animals injected with AAV-NAC32 alone, endogenous ␣Syn protein levels were significantly downregulated in the substantia nigra.

Intracerebral hemorrhage (ICH) occurs when brain blood vessels rupture, causing inflammation and cell death. 2-Fucosyllactose (2FL), a human milk oligosaccharide, has potent antiapoptotic and anti-inflammatory effects. The purpose of this study was to examine the protective effect of 2FL in cellular and rodent models of ICH. Hemin was added to a primary rat cortical neuronal and BV2 microglia coculture to simulate ICH in vitro. IBA1 and MAP2 immunoreactivities were used to determine inflammation and neuronal survival. Hemin significantly increased IBA1, while it reduced MAP2 immunoreactivity. 2FL significantly antagonized both responses. The protective effect of 2FL was next examined in a rat ICH model. Intracerebral administration of type VII collagenase reduced open-field locomotor activity. Early post-treatment with 2FL significantly improved locomotor activity. Brain tissues were collected for immunohistochemistry and qRT-PCR analysis. 2FL reduced IBA1 and CD4 immunoreactivity in the lesioned striatum. 2FL downregulated the expression of ER stress markers (PERK and CHOP), while it upregulated M2 macrophage markers (CD206 and TGFβ) in the lesioned brain. Taken together, our data support that 2FL has a neuroprotective effect against ICH through the inhibition of neuroinflammation and ER stress. 2FL may have clinical implications for the treatment of ICH.