EPO with a retrobulbar administration could protect RGCs from acute elevated IOP.

Neonatal brain injury, especially severe injury induced by hypoxia-ischemia (HI), causes mortality and long-term neurological impairments. Our previous study demonstrated activation of CD11b + myeloid cells, including residential microglial cells (MGs) and infiltrating monocyte-derived macrophages (MDMs) in a murine model of hypoxicischemic brain damage (HIBD), with unknown functions. Here, we study the differences in the phagocytic function of MGs and MDMs to clarify their potential roles after HIBD. HI was induced in 9-10-day postnatal mice. On days 1 and 3 after injury, pathological and neurobehavioral tests were performed to categorize the brain damage as mild or severe. Flow cytometry was applied to quantify the dynamic change in the numbers of MGs and MDMs according to the relative expression level of CD45 in CD11b + cells. CX 3 CR 1 GFP CCR 2 RFP double-transformed mice were used to identify MGs and MDMs in the brain parenchyma after HIBD. Lysosome-associated membrane protein 1 (LAMP1), toll-like receptor 2 (TLR2), CD36, and transforming growth factor (TGF-β) expression levels were measured to assess the underlying function of phagocytes and neuroprotective factors in these cells. The FITC-dextran 40 phagocytosis assay was applied to examine the change in phagocytic function under oxygen-glucose deprivation (OGD) in vitro. We found that neonatal HI induced a different degree of brain damage: mild or severe injury. Compared with mildly injured animals, mice with severe injury had lower weight, worse neurobehavioral scores, and abnormal brain morphology. In a severely injured brain, CD11b + cells remarkably increased, including an increase in the MDM population and a decrease in the MG population. Furthermore, MDM infiltration into the brain parenchyma was evident in CX 3 CR 1 GFP CCR 2 RFP double-transformed mice. Mild and severe brain

While extensive studies report that neonatal hypoxia-ischemia (HI) induces long-term cognitive impairment via inflammatory responses in the brain, little is known about the role of early peripheral inflammation response in HI injury. Here we used a neonatal hypoxia rodent model by subjecting postnatal day 0 (P0d) rat pups to systemic hypoxia (3.5 h), a condition that is commonly seen in clinic neonates, Then, an initial dose of minocycline (45 mg/kg) was injected intraperitoneally (i.p.) 2 h after the hypoxia exposure ended, followed by half dosage (22.5 mg/kg) minocycline treatment for next 6 consecutive days daily. Saline was injected as vehicle control. To examine how early peripheral inflammation responded to hypoxia and whether this peripheral inflammation response was associated to cognitive deficits. We found that neonatal hypoxia significantly increased leukocytes not only in blood, but also increased the monocytes in central nervous system (CNS), indicated by presence of C-C chemokine receptor type 2 (CCR2+)/CD11b+CD45+ positive cells and CCR2 protein expression level. The early onset of peripheral inflammation response was followed by a late onset of brain inflammation that was demonstrated by level of cytokine IL-1β and ionized calcium binding adapter molecule 1(Iba-1; activated microglial cell marker). Interrupted blood-brain barrier (BBB), hypomyelination and learning and memory deficits were seen after hypoxia. Interestingly, the cognitive function was highly correlated with hypoxia-induced leukocyte response. Notably, administration of minocycline even after the onset of hypoxia significantly suppressed leukocyte-mediated inflammation as well as brain inflammation, demonstrating neuroprotection in systemic hypoxia-induced brain damage. Our data provided new insights that systemic hypoxia induces cognitive dysfunction, which involves the leukocyte-mediated peripheral inflammation response.

Hypoxia-ischemia (HI) is one of the most common causes of death and disability in neonates. Currently, the only available licensed treatment for perinatal HI is hypothermia. However, it alone is not sufficient to prevent the brain injuries and/or neurological dysfunction related to HI. Perinatal HI can activate the immune system and trigger the peripheral and central responses which involve the immune cell activation, increase in production of immune mediators and release of reactive oxygen species. There is mounting evidence indicating that regulation of immune response can effectively rescue the outcomes of brain injury in experimental perinatal HI models such as Rice-Vannucci model of newborn hypoxic-ischemic brain damage (HIBD), local transient cerebral ischemia and reperfusion model, perinatal asphyxia model, and intrauterine hypoxia model. This review summarizes the many studies about immunomodulatory mechanisms and therapies for HI. It highlights the important actions of some widely documented therapeutic agents for effective intervening of HI related brain damage, namely, HIBD, such as EPO, FTY720, Minocycline, Gastrodin, Breviscapine, Milkvetch etc. In this connection, it has been reported that the ameboid microglial cells featured prominently in the perinatal brain represent the key immune cells involved in HIBD. To this end, drugs, chemical agents and herbal compounds which have the properties to suppress microglia activation have recently been extensively explored and identified as potential therapeutic agents or strategies for amelioration of neonatal HIBD.

To compare the differences in color Doppler imaging (CDI) and pattern visual evoked potential (P-VEP) examinations between normal tension glaucoma (NTG) and hypertension primary open angle glaucoma (HTG) patients, and investigate the relation between flow velocities measured by CDI and P-VEP examination in NTG and HTG patients. Sixty NTG patients, 66 HTG patients and 44 control subjects underwent CDI evaluation of the ophthalmic artery (OA), short posterior ciliary artery (SPCA) and central retinal arteries (CRA). The peak systolic velocities (PSV) and end-diastolic velocities (EDV) and resistive index (RI) of all retrobulbar vessels were measured. The latency and amplitude of P100 in P-VEP were recorded from the three groups. The differences of CDI and P-VEP parameters among NTG group, HTG group and control group were compared by one-way analysis of variance. The correlations between CDI parameters and visual field indices, P-VEP and visual field indices, P-VEP and CDI parameters in NTG and HTG patients were evaluated by Pearson's correlation analysis. NTG and HTG patients had the lower EDV and higher RI in the OA, CRA and SPCA comparing with that of control subjects. NTG and HTG patients also had lower PSV in OA and CRA comparing with that of control subjects. There was no significant difference in the blood flow velocities and RI of all retrobulbar vessels between NTG and HTG patients. The latency of P100 in VEP delayed and the amplitude of P100 decreased in the NTG and HTG patients comparing with that of the control group. There was no significant difference in the latency and amplitude of P100 between the NTG and HTG patients. The RI of OA and SPCA were negatively correlated with the mean deviation (MD) values in the NTG and HTG patients. The RI of OA was positively correlated with the PSD value in the NTG and HTG patients. The MD values in the NTG and HTG patients were negatively correlated with the latency time of P100. The RI of OA was positively correlated with the latency time of P100 in NTG and HTG patients. The RI of OA was negatively correlated with the amplitude of P100 in HTG patients. No significant difference was found in the parameters of CDI and P-VEP between NTG and HTG patients. The certain parameters of CDI were correlated with P-VEP parameters in NTG and HTG patients.