Effects of Neopterin on Focal Cerebral Ischemia In Rats

Pteridines ◽  
1996 ◽  
Vol 7 (4) ◽  
pp. 157-159
Author(s):  
Toshiyuki Arai ◽  
Hisanari Ishii ◽  
Hiroko Mori ◽  
Kenjiro Mori ◽  
Shuji Kojima

Summary We examined the effects of neopterin on focal cerebral ischemia induced by transient (2 h) occlusion of the middle cerebral artery (MCA) in rats. Neopterin was administered 10 min before reperfusion (3 mg/kg i.p). The ischemic damage was evaluated one week after the MCA occlusion by magnetic resonance imaging (MRI) and by the immunohistochemical reaction for microtubule-associated protein 2 (MAP2). The ischemic lesion detected by MRI was significantly smaller in the neopterin-treated group than in the non-treated group (n=4 in each group, p<0.05). However, the ischemic neuronal damage determined by MAP2 in the neopterintreated group was not significantly different from that in the non-treated group. Since MRI is thought to reflect the distribution of not only neurons but also glial cells, these results may indicate the effects of neopterin on the glial reaction in focal cerebral ischemia.

1998 ◽  
Vol 18 (9) ◽  
pp. 1022-1031 ◽  
Author(s):  
Christian Beaulieu ◽  
Elmar Busch ◽  
Joachim Röther ◽  
Alexander de Crespigny ◽  
Carleton J. C. Hsia ◽  
...  

Nitroxide free radicals are known to protect cells from oxidative damage. Diffusion-weighted and perfusion-weighted magnetic resonance imaging was used to evaluate the effects of polynitroxyl albumin(PNA) in a middle cerebral artery intraluminal suture model of transient focal cerebral ischemia in the rat. Three groups of Sprague-Dawley rats were investigated: (1) PNA(N = 6), (2) human serum albumin (N = 6), and (3) saline (N = 7). The middle cerebral artery was occluded for 2 hours. Treatment was started 30 minutes after induction of ischemia. A total dose of 1% body weight (volume/weight) of PNA (23.5 mg/dL protein and 110 mmol/L nitroxide), albumin (23.5 mg/dL), or saline was injected intravenously at three time points: 0.5% at 0.5 hours, 0.25% at 2 hours (i.e., just before reperfusion), and 0.25% at 4 hours after occlusion. Six sets of diffusion- and perfusion-weighted magnetic resonance images were acquired throughout the 2 hours of ischemia and the 2 hours of reperfusion. The rats were killed at 24 hours, and the brains were stained with 2,3,5-triphenyltetrazolium chloride (TTC). Diffusion-weighted imaging showed that the growth of the ischemic lesion was suppressed in the PNA-treated group. The 4 hours diffusion-weighted imaging-derived hemispheric lesion volume in the PNA-treated group (25% ± 9%) was significantly smaller than that in the saline-treated(43% ± 13%; P = 0.016) or albumintreated groups (38% ± 6%; P = 0.017). A larger difference was observed for the 24-hour TTC-derived lesion volumes in the PNA (8% ± 7%), saline (35% ± 8%; P< 0.001), and albumin (31% ± 6%; P < 0.001) groups. Perfusion-weighted imaging demonstrated a marked improvement in cerebral perfusion in the PNA-treated group during ischemia and reperfusion. In conclusion, treatment with PNA results in an improvement in perfusion and a reduction of infarct volume in a model of transient focal cerebral ischemia in the rat.


1998 ◽  
Vol 18 (9) ◽  
pp. 931-934 ◽  
Author(s):  
Hisanari Ishii ◽  
Toshiyuki Arai ◽  
Shigehiro Morikawa ◽  
Toshiro Inubushi ◽  
Ikuo Tooyama ◽  
...  

Correlation of focal ischemia-induced brain damage evidenced by magnetic resonance imaging (MRI) and by staining with microtubule-associated protein 2 (MAP2) was studied in rats. Ischemia was produced by transient occlusion of the middle cerebral artery (MCAO). The damage was assessed at 6 to 8 hours after MCAO and 1 week later. The area of damage assessed by MRI agreed with that by MAP2 staining at 6 to 8 hours after MCAO, which was smaller ( P < 0.001) than that defined by MAP2 staining 1 week after MCAO. Glial staining indicated that glial infiltration affected the signal intensity of MRI in the area of damage.


1988 ◽  
Vol 8 (1) ◽  
pp. 89-95 ◽  
Author(s):  
John J. Grome ◽  
Gerlinde Gojowczyk ◽  
Wolfgang Hofmann ◽  
David I. Graham

This study was carried out with a recently developed model of focal cerebral ischemia in the rat based on the photochemical induction of thrombotic stroke using the dye Rose Bengal. We examined the change in the volume of the lesion and brain water content, in separate groups of rats, at different times (1, 4, 24, 72, and 168 h) after the induction of the ischemic lesion. The volume of ischemic damage increased rapidly between 1 and 24 h after the ischemic insult and decreased between 24 and 168 h. The lesion at 168 h was significantly larger than that following 1 h of ischemia and similar to that obtained at 4 h, suggesting that the maximum extent of tissue damage (without the involvement of significant edema) was reached within the first 4 h in this model. The enlargement of the lesion after 4 h correlated closely with changes in brain water content.


2004 ◽  
Vol 184 (6) ◽  
pp. 488-495 ◽  
Author(s):  
Adrian J. Lloyd ◽  
I. Nicol Ferrier ◽  
Robert Barber ◽  
Anil Gholkar ◽  
Allan H. Young ◽  
...  

BackgroundEvidence for structural hippocampal change in depression is limited despite reports of neuronal damage due to hypercortisolaemia and vascular pathology.AimsTo compare hippocampal and white matter structural change in demographically matched controls and participants with early-onset and late-onset depression.MethodHigh-resolution volumetric magnetic resonance imaging (MRI) and rating of MRI hyperintensities.ResultsA total of 51 people with depression and 39 control participants were included. Participants with late-onset depression had bilateral hippocampal atrophy compared with those with early-onset depression and controls. Hippocampal volumes did not differ between control participants and those with early-onset depression. Age of depression onset correlated (negatively) with hippocampal volume but lifetime duration of depression did not. Hyperintensity ratings did not differ between groups.ConclusionsResults suggest that acquired biological factors are of greater importance in late-than in early-onset illness and that pathological processes other than exposure to hypercortisolaemia of depression underlie hippocampal atrophy in depression of late life.


2009 ◽  
Vol 29 (5) ◽  
pp. 1048-1058 ◽  
Author(s):  
Robert A Knight ◽  
Kishor Karki ◽  
James R Ewing ◽  
George W Divine ◽  
Joseph D Fenstermacher ◽  
...  

An intravenous step-down infusion procedure that maintained a constant gadolinium-diethylene-triaminepentaacetic acid (Gd-DTPA) blood concentration and magnetic resonance imaging (MRI) were used to localize and quantify the blood-brain barrier (BBB) opening in a rat model of transient cerebral ischemia ( n = 7). Blood-to-brain influx rate constant ( K i) values of Gd-DTPA from such regions were estimated using MRI-Patlak plots and compared with the K, values of Gd-[14C]DTPA, determined minutes later in the same rats with an identical step-down infusion, quantitative autoradiography (QAR), and single-time equation. The normalized plasma concentration-time integrals were identical for Gd-DTPA and Gd-[14C]DTPA, indicating that the MRI protocol yielded reliable estimates of plasma Gd-DTPA levels. In six rats with a BBB opening, 14 spatially similar regions of extravascular Gd-DTPA enhancement and Gd-[14C]DTPA leakage, including one very small area, were observed. The terminal tissue-plasma ratios of Gd-[14C]DTPA tended to be slightly higher than those of Gd-DTPA in these regions, but the differences were not significant. The MRI-derived K i, values for Gd-DTPA closely agreed and correlated well with those obtained for Gd-[14C]DTPA. In summary, MRI estimates of Gd-DTPA concentration in the plasma and brain and the influx rate are quantitatively and spatially accurate with step-down infusions.


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