Long-term l-NAME treatment potentiates the blood–brain barrier disruption during pentylenetetrazole-induced seizures in rats

Kalayci, Rivaze; Kaya, Mehmet; Ahıshalı, Bülent; Arıcan, Nadir; Elmas, İmdat; Küçük, Mutlu

doi:10.1016/j.lfs.2005.12.034

Cited by 11 publications

(4 citation statements)

References 36 publications

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“…Perfusion with 50 ml of PBS (pH 7.2) was followed by 50 ml of the Evans blue cocktail (1% Evans blue and 4% PFA) in PBS. Thus, each mouse received 500 mg of Evans blue (EB), which binds to serum albumin (m r = 65 kDa) [20]. The dissected testes were post-fixed in 4% PFA in PBS overnight at 4°C, followed by immersion in PBS containing 30% sucrose overnight at 4°C for cryoprotection, embedded in OCT cryostat-embedding compound (Tissue-Tek, Torrance, CA, U.S.A) and finally chilled on dry ice and stored at −80°C until further use.…”

Section: Methodsmentioning

confidence: 99%

The Gut Microbiota and Developmental Programming of the Testis in Mice

et al. 2014

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Nutrients and environmental chemicals, including endocrine disruptors, have been incriminated in the current increase in male reproductive dysfunction, but the underlying mechanisms remain unknown. The gastrointestinal tract represents the largest surface area exposed to our environment and thereby plays a key role in connection with exposure of internal organs to exogenous factors. In this context the gut microbiome (all bacteria and their metabolites) have been shown to be important contributors to body physiology including metabolism, cognitive functions and immunity. Pivotal to male reproduction is a proper development of the testis, including the formation of the blood-testis barrier (BTB) that encapsulates and protects germ cells from stress induced environmental cues, e.g. pathogenic organisms and xenobiotics. Here we used specific pathogen free (SPF) mice and germ-free (GF) mice to explore whether gut microbiota and/or their metabolites can influence testis development and regulation of BTB. Lumen formation in the seminiferous tubules, which coincides with the development of the BTB was delayed in the testes of GF mice at 16 days postpartum. In addition, perfusion experiments (Evans blue) demonstrated increased BTB permeability in these same mice. Reduced expressions of occludin, ZO-2 and E-cadherin in GF testis suggested that the microbiota modulated BTB permeability by regulation of cell-cell adhesion. Interestingly, exposure of GF mice to Clostridium Tyrobutyricum (CBUT), which secrete high levels of butyrate, restored the integrity of the BTB and normalized the levels of cell adhesion proteins. Moreover, the GF mice exhibited lower serum levels of gonadotropins (LH and FSH) than the SPF group. In addition, the intratesticular content of testosterone was lower in GF compared to SPF or CBUT animals. Thus, the gut microbiome can modulate the permeability of the BTB and might play a role in the regulation of endocrine functions of the testis.

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Section: Methodsmentioning

confidence: 99%

The Gut Microbiota and Developmental Programming of the Testis in Mice

et al. 2014

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“…BBB permeability was evaluated by measuring extravasation of Evans Blue (EB) dye, 19 which can bind to serum albumin after intravenous injection and, therefore, has been used as a tracer for serum albumin. Briefly, EB dye (2% in saline, 4 mL/kg) was injected intravenously via the tail and allowed to circulate for 3 hours.…”

Section: Evaluation Of Bbb Permeabilitymentioning

confidence: 99%

Peroxisome Proliferator-Activated Receptor-γ Activation With Angiotensin II Type 1 Receptor Blockade Is Pivotal for the Prevention of Blood-Brain Barrier Impairment and Cognitive Decline in Type 2 Diabetic Mice

et al. 2012

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Abstract-We reported previously that an angiotensin II type 1 receptor blocker, telmisartan, improved cognitive decline with peroxisome proliferator-activated receptor-␥ activation; however, the detailed mechanisms are unclear. Enhanced blood-brain barrier (BBB) permeability with alteration of tight junctions is suggested to be related to diabetes mellitus. Therefore, we examined the possibility that telmisartan could attenuate BBB impairment with peroxisome proliferator-activated receptor-␥ activation to improve diabetes mellitus-induced cognitive decline. Type 2 diabetic mice KKA y exhibited impairment of cognitive function, and telmisartan treatment attenuated this. Cotreatment with GW9662, a peroxisome proliferator-activated receptor-␥ antagonist, interfered with these protective effects of telmisartan against cognitive function. BBB permeability was increased in both the cortex and hippocampus in KKA y mice. Administration of telmisartan attenuated this increased BBB permeability. Coadministration of GW9662 reduced this effect of telmisartan. Significant decreases in expression of tight junction proteins and increases in matrix metalloproteinase expression, oxidative stress, and proinflammatory cytokine production were observed in the brain, and treatment with telmisartan restored these changes. Swollen astroglial end-feet in BBB were observed in KKA y mice, and this change in BBB ultrastructure was decreased in telmisartan. These effects of telmisartan were weakened by cotreatment with GW9662. In contrast, administration of another angiotensin II type 1 receptor blocker, losartan, was less effective compared with telmisartan in terms of preventing BBB permeability and astroglial end-foot swelling, and coadministration of GW9662 did not affect the effects of losartan. These findings are consistent with the possibility that, in type 2 diabetic mice, angiotensin II type 1 receptor blockade with peroxisome proliferator-activated receptor-␥ activation by telmisartan may help with protection against cognitive decline by preserving the integrity of the BBB. 1 Impairment of the BBB has been suggested to play a key role in the development and progression of several CNS disorders contributing to cognitive decline.2 Such BBB impairment is mainly caused by hypoxia/ischemia and inflammation. [3][4][5] Type 2 diabetes mellitus (T2DM) has been highlighted as a major risk factor for cognitive decline.6 However, the mechanisms involved are not completely understood. T2DM is characterized by hyperglycemia, hyperinsulinemia, and chronic cerebral microvascular complications. Studies focused on chronic hyperglycemia and increased vascular damage in diabetes mellitus showed that abnormal glucose metabolism results in the generation of reactive oxygen species followed by oxidative stress, mitochondrial dysfunction, and inflammatory response.

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“…To further validate the utility of ZMB741 in the assessment of BBB disruption in living zebrafish, we applied ZMB741 to zebrafish exposed to pentylenetetrazole (PTZ), a proconvulsant that has been widely used to induce seizures in various animal models including zebrafish . It has been shown that the BBB can be disrupted after seizures induced by PTZ . We exposed zebrafish to PTZ for 2 days and stained the zebrafish with ZMB741 by static immersion.…”

Section: Resultsmentioning

confidence: 99%

“…36 It has been shown that the BBB can be disrupted after seizures induced by PTZ. 37 We exposed zebrafish to PTZ for 2 days and stained the zebrafish with ZMB741 by static immersion. In vivo fluorescent imaging of the CBV clearly visualized the extravasation of ZMB741 in zebrafish exposed to PTZ but not in control zebrafish ( Figure 4).…”

mentioning

confidence: 99%

Identification of a Novel Indoline Derivative for in Vivo Fluorescent Imaging of Blood-Brain Barrier Disruption in Animal Models

Nishimura

Yata

Nomoto

et al. 2013

ACS Chem. Neurosci.

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Disruption of the blood-brain barrier (BBB) can occur in various pathophysiological conditions. Administration of extraneous tracers that can pass the disrupted, but not the intact, BBB and detection of the extravasation have been widely used to assess BBB disruption in animal models. Although several fluorescent tracers have been successfully used, the administration of these tracers basically requires intravascular injection, which can be laborious when using small animals such as zebrafish. To identify fluorescent tracers that could be easily administered into various animal models and visualize the BBB disruption in vivo, we prepared nine structurally related indoline derivatives (IDs) as a minimum set of diverse fluorescent compounds. We found that one ID, ZMB741, had the highest affinity for serum albumin and emitted the strongest fluorescence in the presence of serum albumin of the nine IDs tested. The affinity to serum albumin and the fluorescence intensity was superior to those of Evans blue and indocyanine green that have been conventionally used to assess the BBB disruption. We showed that ZMB741 could be administered into zebrafish by static immersion or mice by intraperitoneal injection and visualizes the active disruption of their BBB. These results suggest that ZMB741 can be a convenient and versatile tool for in vivo fluorescent imaging of BBB disruption in various animal models. The strategy used in this study can also be applied to diversity-oriented libraries to identify novel fluorescent tracers that may be superior to ZMB741.

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Long-term l-NAME treatment potentiates the blood–brain barrier disruption during pentylenetetrazole-induced seizures in rats

Cited by 11 publications

References 36 publications

The Gut Microbiota and Developmental Programming of the Testis in Mice

The Gut Microbiota and Developmental Programming of the Testis in Mice

Peroxisome Proliferator-Activated Receptor-γ Activation With Angiotensin II Type 1 Receptor Blockade Is Pivotal for the Prevention of Blood-Brain Barrier Impairment and Cognitive Decline in Type 2 Diabetic Mice

Identification of a Novel Indoline Derivative for in Vivo Fluorescent Imaging of Blood-Brain Barrier Disruption in Animal Models

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