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Ran Liu

Publications and source records attributed to Ran Liu.

28 records · Page 2Linked to original sources
PubMed2004

Transient cerebral ischemia induces aberrant neuronal cell cycle re-entry and Alzheimer's disease-like tauopathy in female rats.

Aberrant mitosis occurs in many tauopathy-related neurodegenerative diseases and is believed to precede the formation of neurofibrillary tangles. In this study, we report for the first time that transient cerebral ischemia induces aberrant mitotic proteins and hyperphosphorylation of tau protein with neurofibrillary tangle-like conformational epitopes in adult female rat cortex. Following transient cerebral ischemia in rats, initiation of apoptosis precedes and is potentially integrated with subsequent aberrant mitosis and tau hyperphosphorylation. Furthermore, inhibition of mitosis-related cyclin-dependent kinases (Cdks) by roscovitine significantly reduced the hyperphosphorylation of tau. Administration of the female sex steroid and potent neuroprotective agent, 17beta-estradiol, reduced ischemia-reperfusion-induced cerebral damage and the subsequent aberrant mitosis and tauopathies. These results provide a neuropathological basis for the higher prevalence of dementia in stroke patients and support the hypothesis that apoptosis and aberrant mitosis are integrated pathological events in neurons that may play a critical role in the development of Alzheimer's disease and other tauopathy-related neuropathology.

Alzheimer Disease↗
PubMed2004

[Application of MEMS microneedles array in biomedicine].

Microneedles array based on micro electro-mechanical system (MEMS) technology is one of important applications in biomedicine and brings a new means in biomedicine field. The prospect for the development of microneedles technology in precision drug injection, clinical monitoring and biochemistry test is and save broad. This paper describes three important applications of MEMS microneedles array in biomedicine field: biomedicine microneedles electrode, transdermal delivery of drugs and fluid extraction, and then summarizes their application elements and recent development. It explains the characteristics of microneedles, which provide painless, effective and save biomedical method in accordance with human requirements. In addition, a series of the fabrication technology of microneedles array is discussed.

Drug Delivery Systems↗
PubMed2003

Quinol-based cyclic antioxidant mechanism in estrogen neuroprotection.

Substantial evidence now exists that intrinsic free-radical scavenging contributes to the receptor-independent neuroprotective effects of estrogens. This activity is inherently associated with the presence of a phenolic A-ring in the steroid. We report a previously unrecognized antioxidant cycle that maintains the "chemical shield" raised by estrogens against the most harmful reactive oxygen species, the hydroxyl radical (*OH) produced by the Fenton reaction. In this cycle, the capture of *OH was shown to produce a nonphenolic quinol with no affinity to the estrogen receptors. This quinol is then rapidly converted back to the parent estrogen via an enzyme-catalyzed reduction by using NAD(P)H as a coenzyme (reductant) and, unlike redox cycling of catechol estrogens, without the production of reactive oxygen species. Due to this process, protection of neuronal cells against oxidative stress is also possible by quinols that essentially act as prodrugs for the active hormone. We have shown that the quinol obtained from a 17beta-estradiol derivative was, indeed, able to attenuate glutamate-induced oxidative stress in cultured hippocampus-derived HT-22 cells. Estrone quinol was also equipotent with its parent estrogen in reducing lesion volume in ovariectomized rats after transient middle carotid artery occlusion followed by a 24-h reperfusion. These findings may establish the foundation for a rational design of neuroprotective antioxidants focusing on steroidal quinols as unique molecular leads.

Animals↗
PubMed2003

Estrogen protects the inner retina from apoptosis and ischemia-induced loss of Vesl-1L/Homer 1c immunoreactive synaptic connections.

PURPOSE: Protective effects of estrogen on nerve cells including retinal neurons have been described previously. However, subcellular effects on synaptic connectivity in mild ischemia more closely resembling ischemic conditions found in diabetic or sickle cell retinopathy and stenosis of the carotid artery have not been identified. The present study quantitatively analyzed effects of estrogen administration on synaptic connections of neurons in the ganglion cell layer (GCL) of the retina. METHODS: Staining of Vesl-1L/Homer 1c (V-1L) immunoreactivity and TUNEL cytochemistry were used to quantify neuroprotective effects at the synaptic level in a model of mild retinal ischemia induced by temporary middle cerebral artery occlusion in the adult rat. RESULTS: V-1L immunoreactivity was found in both synaptic layers, postsynaptic to glutamatergic ribbon synapses. Mild retinal ischemia led to a significantly higher percentage reduction in the number of V-1L-positive synapses in the inner plexiform layer (IPL) compared with the percentage of TUNEL-positive apoptotic neurons in the GCL. Estrogen prevented ischemia-induced loss of V-1L-immunoreactive synapses in the IPL and apoptosis of cells in the GCL. CONCLUSIONS: Immunoreactivity for V-1L can be used as a synaptic marker for early changes before more severe neurodegenerative events. The present results suggest that estrogen protects neurons in the GCL including RGCs from both apoptosis and early changes in synaptic connections associated with ischemia and potentially preceding apoptosis.

Animals↗
PubMed2003

The use of estrogens and related compounds in the treatment of damage from cerebral ischemia.

There are 750,000 new cases of stroke each year in the United States, and brain damage from stroke leads to high health care costs and disabilities. Needed, but currently not available, are therapies that can be administered prior to, during, or after cerebral ischemia that reduce or eliminate neuronal damage from stroke. To address this issue, we began to assess the neuroprotective effects of estrogens and related compounds in stroke neuroprotection to determine whether these compounds had potential for clinical application. First, we demonstrated that 17 beta-estradiol (E2) pretreatment exerted potent neuroprotection of the cerebral cortex over a wide dose range and pretreatment interval. Thereafter, we assessed the ability of a variety of non-feminizing estrogens to protect brain tissue from stroke. We observed that pretreatment with 17 alpha-estradiol, the complete enantiomer of E2 (ENT-E2), 2-adamantylestrone, and the enantiomer of 17-desoxyestradiol, were as effective as E2 in pretreatment protection from stroke damage. These data suggest that non-estrogen receptor mechanisms are involved in brain neuroprotection under our treatment conditions. We then determined whether the observed E2 protection could be extended to times after the onset of the cerebral ischemic event. Using a formulation of E2 that rapidly delivers the steroid, a necessary condition for acute therapy of an ongoing stroke, we demonstrated that 100 mg E2/kg could protect brain tissue for up to 3 h after the onset of the stroke. To determine whether this therapeutic window could be extended with higher doses of the steroid, we conducted a dose-response assessment of E2 when administered at 6 h after the onset of the ischemic event. While the effectiveness of the 100 micro g E2/kg was reduced at this time interval, higher doses of E2 were effective. E2, at doses of 500 and 1000 micro g/kg, reduced infarct volume by more than 50%, even with this 6-h delay in treatment. Collectively, these data indicate that estrogens could prove to be useful therapies in preventing brain damage from strokes.

Animals↗
PubMed2003

[Diagnosis and treatment of cystic acoustic neuroma].

OBJECTIVE: To study the clinical features and treatment of cystic acoustic neuroma. METHODS: Twenty-two patients with cystic acoustic neuromas were diagnosed by CT and MRI preoperatively, and the tumors were resected by retrosigmoid approach, and verified by pathological studies. RESULTS: Of the 22 patients, 18 had tumors totally resected (postoperative house Brackman facial nerve grading: grade II in 4 patients, III in 7, IV in 3, V in 2, VI in 2) and 4 had tumors subtotally resected. CONCLUSION: Because of its specific clinical features and poor operative results, cystic acoustic neuroma should be regarded as a specific subtype.

Adolescent↗
PubMed2002

Testosterone increases neurotoxicity of glutamate in vitro and ischemia-reperfusion injury in an animal model.

Increasing evidence has demonstrated striking sex differences in the outcome of neurological injury. Whereas estrogens contribute to these differences by attenuating neurotoxicity and ischemia-reperfusion injury, the effects of testosterone are unclear. The present study was undertaken to determine the effects of testosterone on neuronal injury in both a cell-culture model and a rodent ischemia-reperfusion model. Glutamate-induced HT-22 cell-death model was used to evaluate the effects of testosterone on cell survival. Testosterone was shown to significantly increase the toxicity of glutamate at a 10 microM concentration, whereas 17beta-estradiol significantly attenuated the toxicity at the same concentration. In a rodent stroke model, ischemia-reperfusion injury was induced by temporal middle cerebral artery occlusion (MCAO) for 1 h and reperfusion for 24 h. To avoid the stress-related testosterone reduction, male rats were castrated and testosterone was replaced by testosterone pellet implantation. Testosterone pellets were removed at 1, 2, 4, or 6 h before MCAO to determine the duration of acute testosterone depletion effects on infarct volume. Ischemic lesion volume was significantly decreased from 239.6 +/- 25.9 mm(3) in control to 122.5 +/- 28.6 mm(3) when testosterone pellets were removed at 6 h before MCAO. Reduction of lesion volume was associated with amelioration of the hyperemia during reperfusion. Our in vitro and in vivo studies suggest that sex differences in response to brain injury are partly due to the consequence of damaging effects of testosterone.

Animals↗
PubMed2002

Neuroprotective effects of a novel non-receptor-binding estrogen analogue: in vitro and in vivo analysis.

BACKGROUND AND PURPOSE: Although estrogens are neuroprotective, hormonal effects limit their clinical application. Estrogen analogues with neuroprotective function but lacking hormonal properties would be more attractive. The present study was undertaken to determine the neuroprotective effects of a novel 2-adamantyl estrogen analogue, ZYC3. METHODS: Cytotoxicity was induced in HT-22 cells by 10 mmol/L glutamate. 17beta-Estradiol (E2) or ZYC3 was added immediately before the exposure to glutamate. Cell viability was determined by calcein assay. The binding of E2 and ZYC3 to human alpha (ERalpha) and beta (ERbeta) estrogen receptors was determined by ligand competition binding assay. Ischemia/reperfusion injury was induced by temporary middle cerebral artery occlusion (MCAO). E2 or ZYC3 (100 microg/kg) was administered 2 hours or immediately before MCAO, respectively. Infarct volume was determined by 2,3,5-triphenyltetrazolium chloride staining. Cerebral blood flow was recorded during and within 30 minutes after MCAO by a hydrogen clearance method. RESULTS: ZYC3 significantly decreased toxicity of glutamate with a potency 10-fold that of E2. ZYC3 did not bind to either ERalpha or ERbeta. Infarct volume was significantly reduced to 122.4+/-17.6 and 83.1+/-19.3 mm(3) in E2 and ZYC3 groups, respectively, compared with 252.6+/-15.6 mm(3) in the ovariectomized group. During MCAO, both E2 and ZYC3 significantly increased cerebral blood flow in the nonischemic side, while no significant differences were found in the ischemic side. However, E2 and ZYC3 significantly increased cerebral blood flow in both sides within 30 minutes after reperfusion. CONCLUSIONS: Our study shows that ZYC3, a non-receptor-binding estrogen analogue, possesses both neuroprotective and vasoactive effects, which offers the possibility of clinical application for stroke without the side effects of estrogens. It also suggests that both the neuroprotective and vasoactive effects of estrogen are receptor independent.

Adamantane↗
PubMedDate not supplied

Ratios of activated matrix metalloproteinase-9 to tissue inhibitor of matrix metalloproteinase-1 in wound fluids are inversely correlated with healing of pressure ulcers.

Previous analyses of fluids collected from chronic, nonhealing wounds found elevated levels of inflammatory cytokines, elevated levels of proteinases, and low levels of growth factor activity compared with fluids collected from acute, healing wounds. This led to the general hypothesis that chronic inflammation in acute wounds produces elevated levels of proteinases that destroy essential growth factors, receptors, and extracellular matrix proteins, which ultimately prevent wounds from healing. To test this hypothesis further, pro- and activated matrix metalloproteinases (MMP-2 and MMP-9), tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2), and the ratios of MMPs/TIMPs were assayed in fluids and biopsies collected from 56 patients with chronic pressure ulcers. Specimens included ulcers treated for 0, 10, and 36 days with conventional therapy or with exogenous cytokine therapies. Quantitative assay data were correlated with the amount of healing. The average MMP-9/TIMP-1 ratio in fluids from 56 ulcers decreased significantly as the chronic pressure ulcers healed. Furthermore, the average MMP-9/TIMP-1 ratio was significantly lower for fluids collected on day 0 from wounds that ultimately healed well (> or =85% reduction in initial wound volume) compared with wounds that healed poorly (< 50% wound volume reduction). These data show that the ratio of MMP-9/TIMP-1 levels is a predictor of healing in pressure ulcers and they provide additional support for the hypothesis that high levels of MMP activity and low levels of MMP inhibitor impair wound healing in chronic pressure ulcers.

Biopsy↗