Errata

In the article “Microvascular Basal Lamina Injury After Experimental Focal Cerebral Ischemia and Reperfusion in the Rat,” by Gerhard F. Hamann, Martin Liebetrau, Helge Martens, Dorothe Burggraf, Christian U. A. Kloss, Gundula Bültemeier, Natalie Wunderlich, Gabriele Jäger, and Thomas Pfefferkorn, published in the May 2002 issue (pp 526–533) of the Journal of Cerebral Blood Flow & Metabolism, an error was overlooked in the Abstract. The correct numbers regarding microvascular damage are given in the Results section, but the Abstract should read as follows: “The ischemic hemisphere showed a reduction of the collagen type IV protein content after ischemia and reperfusion in the Western blot (reduction compared with the nonischemic side: total hemisphere, 33% ± 6%; basal ganglia, 25% ± 7%; cortex, 49% ± 4%; P < 0.01). There was also a decrease in the number of cerebral microvessels in the ischemic and nonischemic hemispheres (20% ± 2%), cortical (8% ± 3%), and basal ganglia areas (31% ± 3%) ( P < 0.001). Besides a reduction of the vessel number, there was also a loss in basal lamina antigen-positive stained area in ischemic areas (hemisphere, 16% ± 3%; cortex, 14% ± 3%; basal ganglia, 21% ± 4%; P < 0.01). …” This change does not influence the interpretation or the conclusions of the paper: microvascular basal lamina damage occurs in rats after experimental cerebral ischemia and reperfusion and is comparable to that observed in nonhuman primates. In addition, the conclusion that microvessel walls in cortical areas are less damaged than those in basal ganglia remains unchanged.

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Microvascular Basal Lamina Injury after Experimental Focal Cerebral Ischemia and Reperfusion in the Rat

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/00004647-200205000-00004 ◽

2002 ◽

Vol 22 (5) ◽

pp. 526-533 ◽

Cited By ~ 86

Author(s):

Gerhard F. Hamann ◽

Martin Liebetrau ◽

Helge Martens ◽

Dorothe Burggraf ◽

Christian U. A. Kloss ◽

...

Keyword(s):

Cerebral Ischemia ◽

Basal Ganglia ◽

Basal Lamina ◽

Collagen Type ◽

Focal Cerebral Ischemia ◽

Collagen Type Iv ◽

Ischemia And Reperfusion ◽

Microvascular Damage ◽

Type Iv ◽

Cerebral Ischemia And Reperfusion

To define the location and extent of microvascular damage of the basal lamina after cerebral ischemia and reperfusion in rats, the authors subjected animals (n = 16) to 3 hours of focal cerebral ischemia and 24 hours of reperfusion using the suture middle cerebral artery occlusion model; sham-operated animals served as controls (n = 6). The Western blot technique was used to define the collagen type IV protein content in various brain regions, whereas immunohistochemistry identified microvascular basal lamina loss (anticollagen type IV staining). The extent of damage was quantified by automatic morphometric video-imaging analysis. Statistical analysis was based on the Mann-Whitney test and the paired Student's t-test. The ischemic hemisphere showed a reduction of the collagen type IV protein content after ischemia and reperfusion in the Western blot (reduction compared with the nonischemic side: total hemisphere, 33% ± 6%; basal ganglia, 49% ± 4%; cortex, 25% ± 7%; P < 0.01). There was also a decrease in the number of cerebral microvessels between the ischemic and nonischemic hemispheres (16% ± 3%), cortical (14% ± 3%), and basal ganglia areas (21% ± 4%) ( P < 0.01). Besides a reduction of the vessel number, there was also a loss in basal lamina antigen-positive stained area in ischemic areas (hemisphere, 20% ± 2%; cortex, 8% ± 3%; basal ganglia, 31% ± 3%; P < 0.001). Cortical areas had a less pronounced basal lamina loss than basal ganglia ( P < 0.05). For the first time, microvascular basal lamina damage, indicated by collagen type IV loss, is proven in rats by biochemical and morphometric analysis. These changes are comparable with those found in nonhuman primates. The authors report novel data regarding microvascular ischemic changes in the cortex. These data provide a basis for future experiments to determine the mechanisms of ischemic microvascular damage and to devise new therapeutic strategies.

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Effects of tissue plasminogen activator on cerebral microvessels of rats during focal cerebral ischemia and reperfusion

Neurological Research ◽

10.1179/016164107x159171 ◽

2007 ◽

Vol 29 (3) ◽

pp. 274-282 ◽

Cited By ~ 17

Author(s):

Dar-Yu Yang ◽

Hung-Chuan Pan ◽

Chun-Jung Chen ◽

Fu-Chou Cheng ◽

Yeou-Chih Wang

Keyword(s):

Cerebral Ischemia ◽

Plasminogen Activator ◽

Tissue Plasminogen Activator ◽

Focal Cerebral Ischemia ◽

Ischemia And Reperfusion ◽

Cerebral Microvessels ◽

Cerebral Ischemia And Reperfusion ◽

Tissue Plasminogen

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P66 Quantification of neuronal and microvascular damage after focal cerebral ischemia and reperfusion

Fibrinolysis and Proteolysis ◽

10.1016/s0268-9499(98)80374-3 ◽

1998 ◽

Vol 12 ◽

pp. 113

Keyword(s):

Cerebral Ischemia ◽

Focal Cerebral Ischemia ◽

Ischemia And Reperfusion ◽

Microvascular Damage ◽

Cerebral Ischemia And Reperfusion

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Recombinant human tissue plasminogen activator protects the basal lamina in experimental focal cerebral ischemia

Thrombosis and Haemostasis ◽

10.1055/s-0037-1613410 ◽

2003 ◽

Vol 89 (06) ◽

pp. 1072-1080 ◽

Cited By ~ 19

Author(s):

Dorothe Burggraf ◽

Helge Martens ◽

Gabriele Jäger ◽

Gerhard Hamann

Keyword(s):

Cerebral Ischemia ◽

Basal Ganglia ◽

Plasminogen Activator ◽

Tissue Plasminogen Activator ◽

Basal Lamina ◽

Collagen Type ◽

Collagen Type Iv ◽

Type Iv ◽

Tissue Plasminogen ◽

Higher Doses

SummaryWhile recombinant tissue plasminogen activator (rt-PA) is successfully used in human ischemic stroke, it may also cause hemorrhagic complications. Animal experiments have shown that hemorrhages are related to microvascular basal lamina damage. We investigated the effects of different doses of rt-PA on the brain microvasculature. Experimental cerebral ischemia in rats was induced for 3 h and followed by 24 h reperfusion (suture model). Each group of rats (n = 6) received either treatment (0.9, 9, or 18 mg rt-PA/kg body weight) or saline (control group) at the end of ischemia. The loss of microvascular basal lamina antigen collagen type IV was measured by Western blot of the ischemic and non-ischemic basal ganglia and cortex. Compared with the contralateral non-ischemic area, collagen type IV was significantly reduced in the ischemic area: (basal ganglia/cortex) 43% +/- 9% / 64% +/- 4 %. Low/moderate doses of rt-PA had a protective effect: 0.9 mg 79% +/- 3% / 89% +/-6%, 9 mg 72% +/- 9%/ 81% +/- 12% (p < 0.05). Higher doses of rt-PA (18 mg) had a similar effect as seen in untreated controls: 57% +/- 11% / 59% +/- 9% (p < 0.05, Anova). MMP-9 and MMP-2, measured by gelatine zymography, steadily increased over higher doses of rt-PA: MMP-9 (basal ganglia/cortex): control 115% +/- 4% / 123% +/- 3% compared with 18 mg rt-PA 146% +/- 5%/ 162% +/- 6% (p < 0.05) and MMP-2: control 109% +/-4%/ 116% +/- 5% and 18 mg rt-PA 222% +/- 15%/ 252% +/- 2% (p < 0.05). Low to moderate doses of rt-PA protect the microvascular basal lamina, whereas high doses of rt-PA have the opposite effect, probably due to increased coactivation of MMP-2 and MMP-9.

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Decrease in Vascular Integrin Immunoreactivity and Selective Loss of Capillaries During Rat Focal Cerebral Ischemia and Reperfusion

Stroke ◽

10.1161/str.32.suppl_1.330-b ◽

2001 ◽

Vol 32 (suppl_1) ◽

pp. 330-330

Author(s):

Christian Ua Kloss ◽

Dorothe Burggraf ◽

Gennadij Raivich ◽

Gerhard F Hamann

Keyword(s):

Cerebral Ischemia ◽

Basal Lamina ◽

Focal Cerebral Ischemia ◽

Specific Interaction ◽

Staining Intensity ◽

Normal Brain ◽

Ischemia And Reperfusion ◽

Selective Loss ◽

Cerebral Ischemia And Reperfusion ◽

Β1 Integrins

80 The β1-integrin cell adhesion molecules are the principal endothelial receptors for basal lamina components like collagen and laminin and contribute to the microvascular integrity. During cerebral ischemia and reperfusion the basal lamina antigens disappear, the vascular permeability is impaired, and edema and petechial hemorrhages develop. The current study investigates the localization of β1-integrins in the normal rat brain and after middle cerebral artery occlusion and reperfusion (MCAO/R). In the normal brain, there was only clear immunoreactivity for the α1, α6 and β1 integrins on endothelia, and for α4 on astrocytes. The α6-immunoreactivity was stronger on larger vessels, while α1β1 stained all vessels similarly. Western blotting confirmed the expression of the integrin subunits. Ultrastructurally, integrins were located on the luminal and on the abluminal side of the endothelia and on perivascular cells. Following 3-hours of cerebral ischemia and reperfusion intervals of 0, 9 and 24 hours (I3R0, I3R9 and I3R24, n=15), the number and staining intensity of immunoreactive vessels in the ischemic area were compared to the contralateral side and classified according to their diameters. There was a moderate reduction in the number of the β1-immunoreactive capillaries (6μm to 9μm) by –12% at I3R0 and –15% at I3R9 that greatly decreased to –43% at I3R24 (all p<0.05), all other vessel sizes remained unaffected. The β1-staining intensity decreased homogeneously over all vessel sizes by –4% to –6% at I3R0, –8% to –12% at I3R9 and –16% to –23% at I3R24 (p<0.05). The vascular staining for α1 was affected similarly but less pronounced. Interestingly, the α6-positive capillaries also were reduced by –21% at I3R24 (p<0.05), but the decrease of the α6-staining intensity was confined to vessels larger than 15μm (–15% at I3R24, p<0.05). The diameter-selective loss of vascular integrin presentation points to a size-specific interaction between the endothelium and the basal lamina. The prominent capillar vulnerability may largely account for the impairment of the microvascular integrity during ischemia and reperfusion.

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