tacrolimus and Cerebral-Infarction

Topics: Alzheimer Disease; Blindness, Cortical; Brain Diseases; Brain Injuries; Cerebral Infarction; Creutzfeldt-Jakob Syndrome; Cyclosporine; Electrodiagnosis; Humans; Immunosuppressive Agents; Occipital Lobe; Seizures; Tacrolimus; Visual Cortex

Topics: Cerebral Infarction; Cyclosporine; Humans; Immunosuppressive Agents; Ligands; Neuroprotective Agents; Stroke; Tacrolimus

The development of a diagnostic technology that can accurately determine the pathological progression of ischemic stroke and evaluate the therapeutic effects of cerebroprotective agents has been desired. We previously developed a novel PET probe, 2-tert-butyl-4-chloro-5-{6-[2-(2-(18)F-fluoroethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin-3-one ([(18)F]BCPP-EF) for detecting activity of mitochondrial complex I (MC-I). This probe was shown to visualize neuronal damage in the living brain of rodent and primate models of neurodegenerative diseases. In the present study, [(18)F]BCPP-EF was applied to evaluate the therapeutic effects of a neuroprotectant, liposomal FK506 (FK506-liposomes), on cerebral ischemia/reperfusion (I/R) injury in transient middle cerebral artery occlusion rats. The PET imaging using [(18)F]BCPP-EF showed a prominent reduction in the MC-I activity in the ischemic brain hemisphere. Treatment with FK506-liposomes remarkably increased the uptake of [(18)F]BCPP-EF in the ischemic side corresponding to the improvement of blood flow disorders and motor function deficits throughout the 7 days after I/R. Additionally, the PET scan could diagnose the extent of the brain damage accurately and showed the neuroprotective effect of FK506-liposomes at Day 7, at which 2, 3, 5-triphenyltetrazolium chloride staining couldn't visualize them. Our study demonstrated that the PET technology using [(18)F]BCPP-EF has a potent capacity to evaluate the therapeutic effect of drug candidates in living brain.

Topics: Animals; Cerebral Infarction; Electron Transport Complex I; Infarction, Middle Cerebral Artery; Liposomes; Male; Motor Activity; Neuroprotective Agents; Positron-Emission Tomography; Rats; Rats, Wistar; Tacrolimus

Topics: Cerebral Arteries; Cerebral Infarction; Female; Humans; Immunosuppressive Agents; Middle Aged; Posterior Leukoencephalopathy Syndrome; Stem Cell Transplantation; Tacrolimus; Transplantation, Homologous; Vasoconstriction

The immunosuppressant FK506 (tacrolimus) is neuroprotective in experimental models of cerebral ischemia. However, the precise mechanisms underlying this neuroprotection remain unknown. In the present study, we hypothesized that FK506 treatment could protect rat brain from oxidative injuries through antioxidative and anti-inflammatory pathways after ischemia-reperfusion injury.. Sprague-Dawley rats were subjected to middle cerebral artery occlusion for 120 minutes, followed by reperfusion. Animals received a single injection of FK506 (0·3 mg/kg) or vehicle intravenously at 30 minutes after ischemic induction. Infarct volume and neurological performance were evaluated at 24 hours after reperfusion. Immunohistochemical analysis for 4-hydroxy-2-nonenal (4-HNE), 8-hydroxy-deoxyguanosine (8-OHdG), ionized calcium-binding adapter molecule 1 (Iba-1), and tumor necrosis factor-alpha (TNF-alpha) were conducted at 24 hours after reperfusion.. FK506 significantly reduced infarct volume (61·7%; P=0·01) and improved neurological deficit scores (P<0·05) 24 hours after reperfusion compared to vehicle. In FK506-treated rats, accumulation of 4-HNE (P<0·01) and 8-OHdG (P<0·01) was significantly suppressed in the cerebral cortex 24 hours after reperfusion. In addition, FK506 markedly reduced microglial activation (P<0·01) and TNF-alpha expression (P<0·01).. These results demonstrate that FK506 may have antioxidant as well as anti-inflammatory effects and reduces ischemic damage following cerebral infarction.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aldehydes; Animals; Antioxidants; Brain; Calcium-Binding Proteins; Cerebral Infarction; Cerebrovascular Circulation; Deoxyguanosine; Disease Models, Animal; Humans; Infarction, Middle Cerebral Artery; Ischemic Attack, Transient; Magnetic Resonance Imaging; Male; Microfilament Proteins; Neuroprotective Agents; Oxidative Stress; Rats; Rats, Sprague-Dawley; Tacrolimus; Tumor Necrosis Factor-alpha

An unusual case of inter-haemispheric disconnection syndrome occurring in a patient who had undergone hepatic transplantation is presented. The underlying disorder, at first wrongly interpreted as encephalitis, was found to be severe, diffuse cerebral vasculitis. The hypothesis that treatment with tacrolimus might have caused, or at least favoured the vascular damage is discussed.

Topics: Brain Damage, Chronic; Cerebral Angiography; Cerebral Infarction; Corpus Callosum; Disability Evaluation; Disease Progression; Fatal Outcome; Humans; Liver Transplantation; Magnetic Resonance Imaging; Male; Middle Aged; Split-Brain Procedure; Tacrolimus; Vasculitis

The immunosuppressant FK506 (1 mg/kg, i.p.) reduces the infarct size following 90 min occlusion of the middle cerebral artery (MCAo) in adult rat brain. Here we have investigated the effect of FK506 on cerebral immune cells that are considered to contribute to neurodegeneration. FK506 substantially attenuated the response of resident and peripheral immune cells following transient ischemia. Between 24 hr and 5 days after MCAo, FK506 reduced the T-cell infiltration in the infarct area as well as the presence of activated and/or phagocytic OX-18, OX-42, GSA-IB4, Iba1, and ED1 positive microglia/macrophages. FK506 also lowered the protein levels of TNFalpha and IL-2 in ischemic brain areas. Repetitive application of FK506 over 20 days attenuated the activation of microglia in the substantia nigra (SN), an area of secondary degeneration. Importantly, FK506 conferred also lasting protection of the neurons of SN; these neurons degenerate by withdrawal of neurotrophic factors from the striatum that undergoes necrotic death as part of the ischemic core. To understand the molecular basis of FK506 effects in cerebral immune cells, we determined in primary postnatal day 0/1 (P0/P1) microglia (i) the expression of the FK506 binding proteins FKBP12, FKBP52, and FKPB65 and (ii) that FK506 (1-100 ng/mL) lowered the number of resting or lipopolysaccharide stimulated microglia as well as we induced the lipopolysaccharide release of TNFalpha in a dose-dependent manner. In summary, FK506 confers rescue of brain tissue following cerebral ischemia not only by neuronal protection, but also by suppression of microglial activation and peripheral immune responses.

Topics: Animals; Biomarkers; Brain Ischemia; Cells, Cultured; Cerebral Infarction; Chemotaxis, Leukocyte; Coculture Techniques; Corpus Striatum; Cytokines; Disease Models, Animal; Encephalitis; Gliosis; Immunosuppressive Agents; Macrophages; Male; Microglia; Nerve Degeneration; Nerve Tissue Proteins; Neuroprotective Agents; Protein Binding; Rats; Rats, Sprague-Dawley; Substantia Nigra; T-Lymphocytes; Tacrolimus

FK-506 confers a neuroprotective effect and is thought to extend the time window for thrombolytic treatment of cerebral ischemia. These effects have not been assessed in an embolic stroke model. In addition, clinical studies have raised concern that FK-506 may increase the risk of hemorrhagic transformation by damaging vascular endothelial cells. We investigated whether combined administration of recombinant tissue plasminogen activator (rt-PA) and FK-506 would extend the therapeutic time window without increasing the hemorrhagic transformation in a rat embolic stroke model. Male Sprague-Dawley rats (n=66) were subjected to embolic infarction and assigned into eight groups. Six of the groups were treated with or without FK-506 (0.3 mg/kg) administration at 60 min after embolization, together with and all six groups received systemic rt-PA administration (10 mg/kg) at 60, 90, or 120 min. Two permanent ischemia groups were administered saline either with or without FK-506. Infarct and hemorrhagic volume were assessed at 24 h after embolization. Diffusion-weighted and perfusion-weighted magnetic resonance imaging (MRI) were performed in the groups administered rt-PA at 90 min and a vehicle control group to assess whether FK-506 influenced the effectiveness of MRI in revealing ischemic lesion. FK-506 extended the therapeutic time window for systemic thrombolysis compared to rt-PA alone without increasing the risk for hemorrhage. Combined therapy with FK-506 salvaged some of the MRI, revealing ischemic lesions destined to infarction in the animals treated by rt-PA alone. Single low dose of FK-506 alone did not ameliorate the embolic infarction, but it did prove effective in extending the therapeutic time windows for thrombolysis without increasing the risk of hemorrhagic transformation.

Topics: Analysis of Variance; Animals; Cerebral Hemorrhage; Cerebral Infarction; Disease Models, Animal; Drug Interactions; Embolism; Immunosuppressive Agents; Male; Rats; Rats, Sprague-Dawley; Stroke; Tacrolimus; Thrombolytic Therapy; Time Factors; Tissue Plasminogen Activator

Immunosuppressant FK506 is neuroprotective in experimental models of cerebral ischemia, but the molecular mechanisms underlying this neuroprotection remain unknown. We have demonstrated that FK506 inhibits the signaling pathways that regulate hypertrophic/proliferative responses in cultured astrocytes. Ischemia/reperfusion injury is associated with the proliferation and hypertrophy of astrocytes and with inflammatory responses. In the present work, we sought to determine whether FK506 neuroprotection after middle cerebral artery occlusion (MCAo) in rat is mediated via suppression of glia activation and changes in cytokine expression. Neurological deficits, infarct size, and astrocyte/microglial response were quantified in rats subjected to 90 min of MCAo. Changes in the mRNA expression of interleukin-1beta (IL-1beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha) in ipsilateral and contralateral cortices were determined by reverse transcription-polymerase chain reaction (RT-PCR). FK506 administered at 1 mg/kg, 60 min after MCAo, produced a significant improvement in neurological function and reduction of infarct volume. In FK506-treated rats, a significant reduction of IL-1beta, IL-6, and TNF-alpha expression was observed 12 h after reperfusion. FK506 neuroprotection was associated with a significant downregulation of IL-1beta expression in astrocytes and microglia in the injured side. FK506 selectively decreased the levels of TNF-alpha, and IL-1beta mRNAs in astrocytes in vitro, with no effect on transforming growth factor-beta 1 (TGF-beta1) and IL-6 expression. Moreover, FK506 inhibits lipopolysaccharide (LPS)-induced activation and cytokine expression in microglia in vitro. Our findings suggest that astrocytes and microglia are targets for FK506, and that modulation of glial response and inflammation may be a mechanism of FK506-mediated neuroprotection in ischemia.

Topics: Animals; Animals, Newborn; Astrocytes; Brain; Cells, Cultured; Cerebral Infarction; Cytokines; Disease Models, Animal; Down-Regulation; Gliosis; Immunosuppressive Agents; Infarction, Middle Cerebral Artery; Interleukin-1; Interleukin-6; Ischemic Attack, Transient; Lipopolysaccharides; Male; Microglia; Neuroglia; Neuroprotective Agents; Rats; Rats, Wistar; Reperfusion Injury; RNA, Messenger; Tacrolimus; Tumor Necrosis Factor-alpha

Topics: Adult; Cerebral Infarction; Female; Humans; Immunosuppressive Agents; Intracranial Hemorrhages; Liver Transplantation; Male; Middle Aged; Tacrolimus

In this study, we administered intraperitoneal magnesium sulfate (90 mg/kg), either alone or in combination with FK506 (0.5 mg/kg) in order to investigate the neuroprotective synergetic effects of both, 30 min before permanent occlusion of the middle cerebral artery (MCA) in gerbil.. Postmortem infarct volume was determined by quantitative image analysis of triphenyltetrazolium-stained brain sections, collected at 1 h, 3 h and 24 h after initiation of cerebral ischemia, to measure consistent infarct volumes of the post -ischemic gerbil brain. Twenty-four male gerbils were intraperitoneally injected with MgSO4 (n=7), FK506 (n=8), or MgSO4 +FK506 (n=9), 30 min before permanent MCA occlusion. The brains of the treated groups were stained at 24 h after initiation of cerebral ischemia.. Significant and consistent infarct volumes (78.3 +/- 3.6 mm3) were observed in the 24 H control group. The infarct volume in the MgSO4 + FK506 group was significantly reduced at each slice, compared to the untreated 24 H control group (P<0.05). Magnesium sulfate reduced total infarct volume by 25.4% (P<0.05), FK506 by 41% (P<0.05), and MgSO4 +FK506 by 50.5% (P<0.05). Also, the infarct volume (38.7 +/- 5.2 mm3) in the MgSO4 + FK506 group was the smallest in all the treated groups, near the volumes seen in the untreated 3H group.. Acute administration of a combination of MgSO4 and FK506 has a synergetic efficacy against brain damage by permanent focal cerebral ischemia.

Topics: Animals; Cerebellum; Cerebral Infarction; Drug Synergism; Gerbillinae; Immunosuppressive Agents; Magnesium Sulfate; Male; Tacrolimus

FK506 (tacrolimus), an immunosuppressant, reportedly reduces ischemic brain injury following transient middle cerebral artery occlusion (MCAO) in rats. The authors previously reported that the therapeutic window of FK506 in this model is more than 1 h, but less than 2 h. The aim of the present study is to determine whether mild hypothermia (35 degrees C) enhances the neuroprotective effects of FK506 and expands its therapeutic window. Sprague-Dawley rats were subjected to 2 h MCAO followed by 24 h reperfusion. Animals were randomly divided into four groups: (I) vehicle-treated normothermic group; (II) FK506-treated normothermic group; (III) vehicle-treated hypothermic group; (IV) FK506-treated hypothermic group. Animals received a single injection of FK506 (0.3 mg/kg) or vehicle intravenously at 2 h after ischemic induction. During ischemia, temporal muscle and rectal temperatures were maintained at 37 degrees C in the normothermic animals and at 35 degrees C in the hypothermic animals. Infarct volumes and neurological performance were evaluated at 24 h after reperfusion. The combination of FK506 and mild hypothermia significantly reduced infarct volume (cortex, -61%; striatum, -31%) and edema volume (cortex, -57%; striatum, -41%), while mild hypothermia or FK506 alone failed to improve ischemic brain damage. Furthermore, this combination also provided for the best functional outcome. These results demonstrate that the combination of FK506 and mild hypothermia significantly reduces ischemic brain damage following transient MCAO in rats, and expands the therapeutic window for FK506. This therapy may be a new approach for treatment of acute stroke.

Topics: Animals; Body Temperature; Brain Edema; Cerebral Infarction; Cerebrovascular Circulation; Hypothermia, Induced; Immunosuppressive Agents; Ischemic Attack, Transient; Laser-Doppler Flowmetry; Male; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Tacrolimus

We investigated the neuroprotective effect of tacrolimus (FK506) on the ischemic cell death with respect to cytochrome c translocation and DNA fragmentation, which are pivotal events in the necrotic and apoptotic signaling pathway, using permanent focal cerebral ischemia in rats. Immunohistochemically, cytochrome c was observed in the cytoplasm as early as 1 h after middle cerebral artery (MCA) occlusion in the infarcted hemisphere. Cytosolic release of cytochrome c after MCA occlusion was also confirmed by Western blot analysis and enzyme immunoassay. Terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling (TUNEL) showed DNA fragmentation evolving in the ipsilateral cortex and the caudate putamen after 3 and 6 h, respectively, following MCA occlusion. Tacrolimus (1 mg/kg, i.v.), administered immediately after MCA occlusion, significantly attenuated the release of cytochrome c in the ischemic region, the number of TUNEL-positive cells in the ischemic penumbra zone, and the size of cortical ischemic lesions. This study demonstrated that tacrolimus ameliorated the accumulation of cytochrome c in the cytosol and the increase of TUNEL-positive cells induced by cerebral ischemia, indicating that the neuroprotective action of tacrolimus on ischemic brain injury caused by permanent focal cerebral ischemia could partially be attributed to the attenuation of the activation of the apoptotic execution machinery.

Topics: Animals; Brain Ischemia; Cerebral Infarction; Cytochromes c; DNA Fragmentation; Immunosuppressive Agents; In Situ Nick-End Labeling; Infarction, Middle Cerebral Artery; Male; Neurons; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Tacrolimus

Topics: Adolescent; Brain; Brain Edema; Cerebral Infarction; Dementia, Vascular; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Magnetic Resonance Imaging; Male; Postoperative Complications; Tacrolimus

Tacrolimus (FK506), an immunosuppressant currently used in clinic, is known to have neuroprotective properties. However, effects in focal ischemia are shown only in a endothelin induced middle cerebral artery (MCA) occlusion model or with filament technique at a relatively high dose. We have previously shown that FK506 had significant protective effects at a low dose of 0.3 mg kg(-1) when administered immediately after ischemia. In this study, we explored the therapeutic time window of FK506 at this low dose, in a transient focal ischemia model using filament technique. Male Sprague-Dawley rats were subjected to 2 h MCA occlusion and subsequent reperfusion. They received FK506 or vehicle (0.3 mg kg(-1)) i.v. at 30, 60 or 120 min after induction of ischemia, and were decapitated 24 h after ischemia. FK506 injected at 30 and 60 min significantly reduced cortical infarction volume (FK506 vs. vehicle; 30 min: 95 +/- 33 mm3 vs. 170 +/- 62 mm3, p < 0.05; 60 min: 93 +/- 45 mm3, vs. 168 +/- 35 mm3, p < 0.05, respectively). FK506 was ineffective when given at 120 min after ischemia. FK506 had no effect on edema formation, nor on the infarct volume in striatum. The therapeutic time window for this low dose of FK506 given i.v. is between 60 and 120 min in this model.

Topics: Animals; Blood Glucose; Brain; Brain Edema; Brain Ischemia; Cardiovascular Physiological Phenomena; Cerebral Infarction; Drug Administration Schedule; Immunosuppressive Agents; Infarction, Middle Cerebral Artery; Male; Neurons; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Tacrolimus; Treatment Outcome

The protective effect of the immunosuppressant agent FK506 in the reperfusion after short-term occlusion of the middle cerebral artery in the rat model was evaluated using [125I]PK-11195 autoradiography. FK506 0.5 mg kg-1 day-1 was administered intramurally to Wistar rats weighing 260-300 g from one day prior to ischemia to seven days after ischemia. Reperfusion was performed after 30 or 60 min occlusion. Infarct area was evaluated by [125I]PK-11195 autoradiography on the seventh day following occlusion. FK506 significantly reduced the infarct area in the caudate nucleus following 30 and 60 min occlusion, but significantly reduced the infarct area in the cortex only following 60 min occlusion. These results suggest that FK506 has a protective effect against reperfusion after short-term occlusion of the middle cerebral artery.

Topics: Animals; Autoradiography; Cerebral Infarction; Disease Models, Animal; Iodine Radioisotopes; Ischemic Attack, Transient; Isoquinolines; Male; Middle Cerebral Artery; Neuroprotective Agents; Rats; Rats, Wistar; Reperfusion; Tacrolimus

The neuroprotective properties of drugs binding to FKBP12, with and without subsequent inhibition of calcineurin, were investigated in rat models of ischemic embolic stroke. Drug effects on brain infarct volumes evoked by transient middle cerebral artery occlusion (MCAO) and by permanent MCAO were determined in vivo by T2-weighted magnetic resonance imaging and post mortem by triphenyltetrazolium chloride staining and histology. Drugs binding to FKBP12 and inhibiting calcineurin, such as FK506 and SDZ ASM 981, dose dependently reduced the infarct volumes, determined 48 h after MCAO by both magnetic resonance imaging and triphenyltetrazolium chloride staining but only in the transient MCAO model. In vivo potencies to reduce brain infarcts paralleled the in vitro potencies to inhibit calcineurin. Histological staining after 6 days of survival showed that the neuroprotective effects were permanent. Rapamycin, known to bind with similar affinity to FKBP12 but not to inhibit calcineurin, was not neuroprotective but abolished the neuroprotective effects of FK506 when coadministered. In the permanent MCAO models, FK506 showed no effect when injected before and little effect when injected after MCAO. Measurements of core temperatures after MCAO in controls and drug-treated rats do not support hypothermia being the mechanism responsible for neuroprotection. We conclude that drugs inhibiting calcineurin activity are neuroprotective in focal cerebral ischemia/reperfusion but not in permanent ischemia models, possibly by preventing reperfusion injury.

Topics: Animals; Arterial Occlusive Diseases; Calcineurin Inhibitors; Cerebral Arteries; Cerebral Infarction; Dose-Response Relationship, Drug; Enzyme Inhibitors; Immunosuppressive Agents; Ischemic Attack, Transient; Magnetic Resonance Imaging; Male; Neuroprotective Agents; Rats; Rats, Inbred SHR; Reperfusion Injury; Tacrolimus

Previous studies have demonstrated that the immunosuppressant FK506 provides neuroprotection in experimental brain injury and suggest that this action may be mediated by suppression of neuronal nitric oxide synthase activation that occurs after ischemic depolarization. We sought to determine whether FK506 reduces histological injury after middle cerebral artery occlusion (MCAO) in the rat and whether the neuroprotective effect is mediated via suppression of in vivo nitric oxide (NO) production during ischemia or early reperfusion.. Under controlled conditions of normoxia, normocarbia, and normothermia, halothane-anesthetized male Wistar rats were subjected to 2 hours of MCAO by the intraluminal occlusion technique in a blinded, randomized experimental trial. Ipsilateral parietal cortical laser-Doppler flowmetry was monitored throughout ischemia. Animals were randomly assigned to 4 pretreatment groups: intravenous FK506 0.3 mg/kg or 1. 0 mg/kg, vehicle (cremaphor), or an equivalent volume of saline administered 30 minutes before MCAO. Infarction volume was assessed by a triphenyltetrazolium chloride staining at 22 hours of reperfusion. In separate experiments, microdialysis probes were placed bilaterally into the striatum. Rats were perfused with artificial cerebrospinal fluid containing 3 micromol/L [14C]- L-arginine for 3 hours and then subjected to 2 hours of right MCAO. Intravenous 0.3 mg/kg FK506 or cremaphor was given 30 minutes before right MCAO. Right-left differences between [14C]-L-citrulline in the effluent were assumed to reflect differences in NO production.. All values are mean+/-SE. FK506 at 0.3 mg/kg reduced infarction volume in cortex: 40+/-12 mm3 compared with saline (109+/-15 mm3) and cremaphor vehicle (148+/-23) (P<0.05). Striatal infarction was also reduced by low-dose FK506: 16+/-4 mm3 versus 36+/-4 mm3 and 34+/-4 mm3 in saline and vehicle groups, respectively (P<0.05). High-dose treatment reduced infarction volume in cortex (61+/-14 mm3, P<0.05 from saline and vehicle groups) and in striatum (22+/-5 mm3, P<0.05 from saline and vehicle groups). [14C]-L-citrulline recovery via microdialysis was markedly enhanced in ischemic compared with nonischemic striatum. However, ischemia-evoked [14C]-L-citrulline recovery was not different in FK506-treated rats compared with vehicle-treated animals.. These data demonstrate that FK506 provides robust neuroprotection against transient focal cerebral ischemia in the rat. The mechanism of protection in vivo is not through attenuation of ischemia-evoked NO production during MCAO and early reperfusion.

Topics: Animals; Cerebral Infarction; Corpus Striatum; Ischemic Attack, Transient; Male; Neuroprotective Agents; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type I; Rats; Rats, Wistar; Reperfusion Injury; Tacrolimus; Time Factors

In the present experiments, we compared the anti-ischemic effects of the immunosuppressants cyclosporin A (CsA) and FK506 in hyperglycemic animals subjected to 30 min of middle cerebral artery (MCA) occlusion. Both immunosuppressants were given as pre-treatment, the effect of treatment being evaluated by 2,3, 5-triphenyltetrazolium (TTC) staining after 3 days of recovery. Both FK506 and CsA reduced the infarct volume to less than 1/3 of control. In spite of CsA's known effect as a blocker of the mitochondrial transition (MPT) pore, it failed to give a more robust effect than FK506. If anything, FK506, which lacks an effect on the MPT pore, had a more pronounced anti-ischemic effect. We conclude that, in this model of infarction, an MPT may not play a major pathogenetic role.

Topics: Analysis of Variance; Animals; Arterial Occlusive Diseases; Cerebral Infarction; Cyclosporine; Hyperglycemia; Immunosuppressive Agents; Ischemic Attack, Transient; Male; Neuroprotective Agents; Rats; Rats, Wistar; Tacrolimus; Treatment Outcome