Background and Purpose-The cellular mechanisms of degeneration and repair preceding rupture of the saccular cerebral artery aneurysm wall need to be elucidated for rational design of growth factor or drug-releasing endovascular devices. Methods-Patient records, preoperative vascular imaging studies, and the snap-frozen fundi resected after microsurgical clipping from 66 aneurysms were studied. Immunostainings for markers of smooth muscle cell (SMC) phenotype, proliferation, and inflammatory cell subtypes and TUNEL reaction were performed. Results-Unruptured (24) and ruptured (42) aneurysms had similar dimensions (median diameter in unruptured 6 mm; median in ruptured 7 mm; Pϭ0.308). We identified 4 basic types of aneurysm wall that associated with rupture: (1) endothelialized wall with linearly organized SMCs (17/66; 42% ruptured), (2) thickened wall with disorganized SMCs (20/66; 55% ruptured), (3) hypocellular wall with either myointimal hyperplasia or organizing luminal thrombosis (14/66; 64% ruptured), and (4) an extremely thin thrombosis-lined hypocellular wall (15/66; 100% ruptured). Apoptosis, de-endothelialization, luminal thrombosis, SMC proliferation, and T-cell and macrophage infiltration associated with rupture. Furthermore, macrophage infiltration associated with SMC proliferation, and both were increased in ruptured aneurysms resected Ͻ12 hours from rupture, suggesting that these were not just reactive changes. Conclusions-Before rupture, the wall of saccular cerebral artery aneurysm undergoes morphological changes associated with remodeling of the aneurysm wall. Some of these changes, like SMC proliferation and macrophage infiltration, likely reflect ongoing repair attempts that could be enhanced with pharmacological therapy.

The computer-controlled thermal therapy system was effective at regulating heating, eliminating carbonization and vaporization, and protecting fiberoptic applicators. MRTI estimation of thermal dose accurately predicted achieved thermal necrosis.

These data suggests that complement activation and MAC formation are involved in SCAA wall degeneration and rupture.

Purpose: To evaluate MRI-based techniques for visual guidance, thermal monitoring, and assessment during transurethral ultrasound thermal therapy of implanted tumors in an in vivo canine prostate model. Materials and Methods:Transmissible venereal tumors (TVT) were grown in the right lobe of the prostate in four dogs. High-temperature thermal therapy was selectively applied to the tumor-bearing lobe using a transurethral ultrasound applicator with a 180°directional heating pattern. Temperature-sensitive MRI (MRTI) using a fast interleaved gradient-echo echo-planar (iGE-EPI) imaging sequence was used for cumulative thermal dose calculations in multiple image planes during the treatment. The results from MRTI-based dose maps and post-treatment MRI were compared to those from histologic analysis.Results: MRTI monitoring in multiple planes across the prostate guided the use and control of a directive ultrasound applicator for the selective ablation of the sections of the prostate that contained implanted tumors. Findings in gadolinium enhanced MRI obtained immediately after thermal therapy slightly underestimated the size of tissue necrosis after treatment, as verified by histopathologic analysis. Conclusion:The use of multiplanar MRTI with a transurethral ultrasound applicator shows significant potential for selective thermal ablation of prostate tumor and tissue.

The expression of mRNAs for a transition protein (TP1) and two variants of protamines (P1 and P2) during rat and mouse spermiogenesis was investigated using cDNA hybridization techniques. Slot-blot analyses from 1-mm segments of seminiferous tubules and in situ hybridization from testis sections showed that the levels of mRNA for TP1 increased in step-7 round spermatids at substage VIIb of the seminiferous epithelial cycle, earlier than that of P1 and P2 at substage VIIc. The mRNA levels of all transcripts remained high during steps 8-13 in both species. In the rat, the mRNA of TP1 disappeared during step 14 between substages XIVa and XIVb. The P1 mRNA levels decreased during steps 15-16 (stages I-III) and the P2 mRNA during step 15 (stage I). In the mouse, TP1 mRNA disappeared during step 13 (stage I). The P1 mRNA level decreased before P2 in step 14 (stage II), whereas P2 was detected up to step 15 (stage V). Northern-blot analyses with all three cDNA probes revealed two sizes of mRNA and their stage-specific expression. The shorter transcripts appeared later than the longer ones, at the steps of spermiogenesis where translation is known to begin. The results suggest that transcription of TP1, P1, and P2 mRNAs starts at specifically defined times during spermiogenesis and that the temporal translational regulation of these mRNAs is different.

The dose and time response of LBNF1, rat testis to gamma irradiation was studied with use of single doses from 2.5 Gy to 6.0 Gy. Germ cells were initially depleted as a result of killing the radiosensitive differentiating spermatogonia. Some recovery of spermatogenesis was observed at 4 and 6 wk after irradiation as indicated by the repopulation of tubules with germ cells derived from surviving stem spermatogonia. Although spermatogenesis showed additional recovery and was maintained throughout the 60-wk follow-up period after 2.5 Gy, at doses from 3.5 Gy to 6.0 Gy, repopulation indices declined after 6 wk to less than 2%. The numbers of Sertoli cells per nonrepopulating tubule were constant, independent of radiation dose or time. In addition, the nonrepopulating tubules contained an average of one A spermatogonium per 100 Sertoli cells. The size and shape of these cells corresponded to undifferentiated A spermatogonia in nonirradiated control tests. Despite high labeling (40%) and mitotic (20%) indices, the numbers of A spermatogonia changed very little with time, and no differentiated cells were produced in these tubules. The failure of spermatogenesis to recover was not due to hormone deficiency: serum gonadotropin levels increased after irradiation, and serum testosterone remained at control levels. The irradiated LBNF1 rat model may be useful for studying the regulation of differentiation of A spermatogonia.

The advances in diagnostic methods (digital subtraction angiography, CT, and MRI) increased the detection rate of DAVFs, and as treatment modalities developed, the results of treatment and outcome of patients markedly improved with the introduction of endovascular techniques and stereotactic radiosurgery. Microsurgery is of limited use in DAVFs resistant to other treatment modalities.

VEGF, TGFbeta, and basic fibroblast growth factor receptors were associated with SCAA wall remodeling, making them potential targets for bioactive endovascular implants or drug therapy aiming to reinforce the SCAA wall.