scholarly journals Upregulation of MAP1B and MAP2 in the Rat Brain after Middle Cerebral Artery Occlusion: Effect of Age

1999 ◽  
Vol 19 (4) ◽  
pp. 425-434 ◽  
Author(s):  
Aurel Popa-Wagner ◽  
Eike Schröder ◽  
Harald Schmoll ◽  
Lary C. Walker ◽  
Christoff Kessler

Although stroke in humans usually afflicts the elderly, most experimental studies on the nature of cerebral ischemia have used young animals. This is especially important when studying restorative processes that are age dependent. To explore the potential of older animals to initiate regenerative processes after cerebral ischemia, the authors studied the expression of the juvenile-specific cytoskeletal protein, microtubule-associated protein (MAP) 1B, and the adult-specific protein, MAP2, in male Sprague-Dawley rats at 3 months and 20 months of age. The levels of MAP1B and MAP2 transcripts and the corresponding proteins declined with increasing age in the hippocampus. In the cortex, the levels of the transcripts did not change significantly with age, but the morphologic features of immunostained fibers were clearly affected by age; that is, cortical MAP1B fibers became thicker, and MAP2 fibers, more diffuse, in aged rats. Focal cerebral ischemia, produced by reversible occlusion of the right middle cerebral artery, resulted in a large decrease in the expression of both MAP1B and MAP2 in the infarct core at the messenger ribonucleic acid and protein levels. However, at 1 week after the stroke, there was vigorous expression of MAP1B and its messenger ribonucleic acid, as well as MAP2 protein, in the border zone adjacent to the infarct of 3-month-old and 20 month-old male Sprague-Dawley rats. The upregulation of these key cytologic elements generally was diminished in aged rats compared with young animals, although the morphologic features of fibers in the infarct border zone were similar in both age groups. These results suggest that the regenerative potential of the aged rat brain appears to be competent, although attenuated, at least with respect to MAP1B and MAP2 expression up to 20 months of age.

2008 ◽  
Vol 29 (3) ◽  
pp. 596-605 ◽  
Author(s):  
Yangdong He ◽  
Ya Hua ◽  
Wenquan Liu ◽  
Haitao Hu ◽  
Richard F Keep ◽  
...  

This study examined whether neuronal hemoglobin (Hb) is present in rats. It then examined whether cerebral ischemia or ischemic preconditioning (IPC) affects neuronal Hb levels in vivo and in vitro. In vivo, male Sprague-Dawley rats were subjected to either 15 mins of transient middle cerebral artery occlusion (MCAO) with 24 h of reperfusion, an IPC stimulus, or 24 h of permanent MCAO (pMCAO), or IPC followed 3 days later by 24 h of pMCAO. In vitro, primary cultured neurons were exposed to 2 h of oxygen—glucose deprivation (OGD) with 22 h of reoxygenation. Results showed that Hb is widely expressed in rat cerebral neurons but not astrocytes. Hemoglobin expression was significantly upregulated in the ipsilateral caudate and the cortical core of the middle cerebral artery territory after IPC. Hemoglobin levels also increased more in the penumbral cortex and the contralateral hemisphere 24 h after pMCAO, but expressions in the ipsilateral caudate and the cortical core area were decreased. Ischemic preconditioning modified pMCAO-induced brain Hb changes. Neuronal Hb levels in vitro were increased by 2 h of OGD and 22 h of reoxygenation. These results indicate that Hb is synthesized in neurons and can be upregulated by ischemia.


2000 ◽  
Vol 20 (11) ◽  
pp. 1537-1549 ◽  
Author(s):  
Susan A. Lyons ◽  
Andrea Pastor ◽  
Carsten Ohlemeyer ◽  
Oliver Kann ◽  
Frank Wiegand ◽  
...  

The authors investigated the time course of leukocyte infiltration compared with microglial activation in adult rat brain slices after permanent middle cerebral artery occlusion (MCAO). To distinguish peripheral leukocytes from microglia, the blood cells were prelabeled in vivo with Rhodamine 6G (Rhod6G) IV before induction of ischemia. At specific times after infarct, invading leukocytes, microglia, and endothelial cells were labeled in situ with isolectin (IL)B4-FITC (ILB4). Six hours after MCAO only a few of the ILB4+ cells were colabeled by Rhod6G. These cells expressed the voltage-gated inwardly and outwardly rectifying K+ currents characteristic of macrophages. The majority of the ILB4+ cells were Rhod6G− and expressed a lack of voltage-gated channels, recently described for ramified microglial cells in brain slices, or exhibited only an inward rectifier current, a unique marker for cultured (but unstimulated) microglia. Forty-eight hours after MCAO, all blood-borne and the majority of Rhod6G− cells expressed outward and inward currents indicating that the intrinsic microglial population exhibited physiologic features of stimulated, cultured microglia. The ILB4+/Rhod6G− intrinsic microglial population was more abundant in the border zone of the infarct and their morphology changed from radial to ameboid. Within this zone, the authors observed rapidly migrating cells and recorded this movement by time-lapse microscopy. The current findings indicate that microglial cells acquire physiologic features of leukocytes at a later time point after MCAO.


1995 ◽  
Vol 15 (3) ◽  
pp. 398-408 ◽  
Author(s):  
Hiroshi Yao ◽  
Myron D. Ginsberg ◽  
David D. Eveleth ◽  
Joseph C. LaManna ◽  
Brant D. Watson ◽  
...  

To ascertain the tempo of progression to irreversible injury in focal ischemia, we subjected halothaneanesthetized Sprague–Dawley rats to photochemically induced distal middle cerebral artery occlusion (dMCAO) combined with permanent ipsilateral and 1 h contralateral common carotid artery occlusions. Head temperature was maintained at 36°C. At times centered at either 1.5 or 3 h post-dMCAO, the rate of local glucose metabolism (lCMRgl) was measured by 2-deoxyglucose autoradiography, and cytoskeletal proteolysis was assessed regionally by an immunoblotting procedure to detect spectrin breakdown products. At 1.5 h (n = 5), the cortical ischemic core was already severely hypometabolic (lCMRgl 15.5 ± 10.8 μmol 100 g−1 min−1, mean ± SD), whereas the cortical penumbral zone was hypermetabolic (69.0 ± 9.7). (The lumped constant was verified to be unchanged by methylglucose studies.) Neutral red pH studies at this time point showed that both the core and penumbral zones were equally acidotic. By 3 h post-dMCAO (n = 6), lCMRgl in the penumbral zone had fallen to low levels (15.4 ± 2.2 μmol 100 g−1 min−1) equal to those of the ischemic core (16.7 ± 4.5). Correspondingly, spectrin breakdown in the ischemic core was advanced at both 2 and 3.5 h post-dMCAO (36 ± 18% and 33 ± 18% of total spectrin, respectively), whereas in the penumbral zone spectrin breakdown was less extensive and more highly variable at both times (22 ± 23% and 29 ± 16%). We conclude that irreversible deterioration of the ischemic core, as evidenced by the onset of local cytoskeletal proteolysis, begins within 2 h of middle cerebral artery occlusion. In the ischemic penumbra, the transition from glucose hyper- to hypometabolism occurs by 3.5 h and is associated with a milder and more variable degree of spectrin breakdown.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Teppei Komatsu ◽  
Hiroki Ohta ◽  
Junichi Hata ◽  
Haruhiko Motegi ◽  
Koshiro Terawaki ◽  
...  

Background: The failure of clinical trials on neuroprotective treatment may be partially caused by unestablished animal models. To verify a trans-arterial regeneration therapy, our project is aimed at developing a brand-new focal stroke model using micro catheter. Methods: Using Sprague-Dawley rats (n=8), a micro catheter (ID 0.26mm, OD 0.35mm) was navigated from the caudal ventral artery to the middle cerebral artery in order to establish local occlusion under digital subtraction angiography apparatus. Results: We succeeded in brain angiography by percutaneous tail artery puncture and occlusion of the middle cerebral artery by a radiopaque micro bead with 6 rats (75%). Ischemic stroke lesion volume is 480.3 mm3±84.2 mm3 on sustained 1% TTC solution after 24 hours occlusion. Conclusion: We present a new rat model for focal stroke using micro catheter under fluoroscopic control. The model is capable of repeated super selective administration of therapeutics directly to cerebral artery, and practice the 3Rs principles in experimental animals because of minimal invasive.Figure Legend- A: A sheath is inserted through the ventral midline, approximately 5 cm from the root of the tail of the rat, with a sharp angle. B: Cerebral angiography of rats. Arrowhead pointe middle cerebral artery. C: Occlusion of the middle cerebral artery by a radiopaque micro bead (arrowhead). D: Brain is sliced and stained 1% TTC solution after 24 hours occlusion.


2015 ◽  
Vol 588 ◽  
pp. 137-141 ◽  
Author(s):  
Nik Nasihah Nik Ramli ◽  
Nursyazwani Omar ◽  
Andrean Husin ◽  
Zalina Ismail ◽  
Rosfaiizah Siran

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