A Single-Center Experience of Mechanical Thrombectomy for Cancer-Associated Ischemic Stroke.

Objectives: Cancer-associated ischemic stroke tends to extend over multiple vascular territories and develops under poor general conditions. Owing to the rarity of such cases and poor prognoses, no comprehensive studies on mechanical thrombectomy for cancer-associated ischemic stroke have been reported in Japan. The present study investigated the radiological and clinical characteristics of mechanical thrombectomy in patients with cancer-associated ischemic stroke at our institution. Methods: We retrospectively reviewed 108 patients who underwent mechanical thrombectomy for large cerebral artery occlusion between January 1, 2021, and October 31, 2022, at our institution. The characteristics of mechanical thrombectomy in the cancer-associated ischemic stroke group were compared with those in the control group. Results: Of the 108 patients (112 procedures), seven patients (eight procedures) with clinically diagnosed cancer-associated ischemic stroke underwent mechanical thrombectomy. Of the eight procedures, six were performed during hospitalization. In contrast, only 10 of 104 procedures were performed in the control group. The in-hospital onset rate was higher in the cancer-associated ischemic stroke group (75.0%) compared to that in the controls (9.6%); p <0.001. The puncture-to-reperfusion time was significantly longer in the cancer-associated ischemic stroke group in comparison to that in the controls with a median interquartile range of 69 minutes (60.0-82.0 minutes) and 59.5 minutes (44.5-69.3 minutes), respectively (p <0.01). However, the rates of successful recanalization defined as thrombolysis in cerebral infarction ≥2b were not significantly different between the cancer-associated ischemic stroke group and controls with values of 62.5% and 79.8%, respectively (p = 0.250). Of the eight cases in the cancer-associated ischemic stroke group, only one (12.5%) had a good outcome on a modified Rankin Scale score of 0 to 2 at discharge, in contrast to 23 of the 104 (23.1%) cases in the controls (p = 0.523). Histopathological examination of six retrieved thrombi in the cancer-associated stroke group using hematoxylin and eosin staining revealed that only one case showed an erythrocyte-dominant thrombus while five displayed a fibrinoplatelet-dominant component. Conversely, 65 of 92 retrieved thrombi in the control group were erythrocyte dominant. Cancer was pathologically diagnosed in four of seven patients, all of which were adenocarcinomas. Conclusion: Cancer-associated ischemic stroke tends to occur during hospitalization. Coagulation disorders associated with cancer, especially adenocarcinoma, may be related to the formation of thrombi with fibrinoplatelet-dominant components, leading to ischemic stroke. The procedural time for mechanical thrombectomy in cancer-associated ischemic stroke tends to be longer.

Short- versus long-term Dual AntiPlatelet Therapy for Stent-Assisted treatment of CErebral aneurysm (DAPTS ACE): a multicenter, open-label, randomized clinical trial.

BACKGROUND: The optimal duration of dual antiplatelet therapy (DAPT) after stent-assisted coil embolization (SACE) for cerebral aneurysm remains uncertain. This randomized trial of short- versus long-term Dual AntiPlatelet Therapy for Stent-Assisted treatment of CErebral aneurysm (DAPTS ACE) aimed to clarify whether long-term DAPT can reduce the occurrence of ischemic stroke in patients with cerebral aneurysms treated by SACE compared with short-term DAPT. METHODS: Patients treated for cerebral aneurysm with SACE were enrolled from 17 hospitals in Japan. Patients were enrolled within 30 days after SACE and assigned in a 1:1 ratio to receive long-term (12 months) or short-term (3 months) DAPT with aspirin and clopidogrel. Randomization was performed centrally through a web-based system. The primary outcome was the time to ischemic stroke event during 3 to 12 months after SACE. This trial was registered with the Japan Registry of Clinical Trials (jRCTs051180141). RESULTS: A total of 142 patients were recruited from November 4, 2016 to January 7, 2019. Among them, 65 and 68 patients assigned to the long- and short-term DAPT groups, respectively, were included in the full analysis set. Ischemic stroke occurred in no patients in the long-term DAPT group and in one patient in the short-term DAPT group. The incidence rate did not differ between the groups (0.0 vs 2.1/100 person-years; log rank test, P=0.33). CONCLUSIONS: In this multicenter randomized controlled trial, there was not a statistically significant difference in the rate of ischemic strokes between long- and short-term DAPT.

Relation between duration of dual antiplatelet therapy and risk of ischemic stroke after stent-assisted treatment of cerebral aneurysm (DAPTS ACE-registry).

BACKGROUND: The optimal duration of dual antiplatelet therapy (DAPT) in patients with cerebral aneurysm who undergo stent-assisted coil embolization (SACE) has not been established. We aimed to clarify the association between duration of DAPT and incidence of ischemic stroke in patients with cerebral aneurysm. METHODS: We registered patients with cerebral aneurysm who underwent SACE in 27 hospitals in Japan. Those treated with DAPT (aspirin and clopidogrel) were eligible for inclusion in a previously reported randomized control trial (RCT). Patients who were ineligible or refused to participate to the RCT were followed-up for 15 months after SACE as the non-RCT cohort. Our study examined both the RCT and non-RCT cohorts. The primary and secondary outcomes were ischemic stroke and hemorrhagic events. RESULTS: Among the 313 patients registered, 296 were included for analysis (of these, 136 were RCT patients and 160 were non-RCT patients). Patients who were treated with DAPT for more than 6 months (n=191) were classified as the long-term DAPT group. Those treated less than 6 months (n=105) were classified as the short-term group. The incidence of ischemic stroke did not significantly differ between the long-term group (2.5 per 100 person-years) and the short-term group (3.2 per 100 person-years); nor did incidence of hemorrhagic events (0.8 and 3.2 per 100 person-years, respectively). The period of DAPT was not significantly associated with incidence rates of ischemic stroke or hemorrhagic events. CONCLUSIONS: Duration of DAPT was not associated with the incidence of ischemic stroke in the first 15 months after SACE.

[Unruptured Intracranial Aneurysms:Endovascular Techniques and Devices:New Devices for Unruptured Intracranial Aneurysms].

Factors causing the formation and growth of intracranial aneurysms include injury and congenital vulnerability of the arterial wall. Therefore, coil embolization of the saccular and fusiform components of intracranial aneurysms is not always curative, and the risk of recurrence in the long-term follow-up is high. Recently, flow diverters(e.g., pipeline, FRED, and Surpass Streamline)and an intrasaccular flow disruptor(W-EB)have been introduced as alternative embolic devices for intracranial aneurysms. These devices can repair arterial walls through neointimal formation surrounding the aneurysm neck and achieve complete cure. The PulseRider is a type of neck bride stent for bifurcation aneurysms that can effectively prevent coil herniation into the parent artery.

Clinical trial of carotid artery stenting using dual-layer CASPER stent for carotid endarterectomy in patients at high and normal risk in the Japanese population.

BACKGROUND: The dual-layer nitinol CASPER stent was designed to prevent plaque prolapse into its strut and periprocedural stroke. OBJECTIVE: To conduct a clinical trial for government approval of the device in patients at either high or normal risk for carotid endarterectomy (CEA). METHODS: Eligible patients had ≥50% symptomatic stenosis or ≥80% asymptomatic stenosis according to the North American Symptomatic Carotid Endarterectomy Trial methods (peak systolic velocity 130 and 230 cm/s on ultrasonography, respectively). The primary endpoint was the lack of major adverse events (MAEs), defined as death, stroke, and myocardial infarction within 30 days, and ipsilateral stroke within 1 year. The performance goal was set at 90.5%. MAE rates were also compared between the CEA high- and normal-risk groups. RESULTS: 140 carotid artery stenting procedures, including 40% of patients at high risk and 60% at normal risk for CEA, were performed in 13 institutes. MAEs occurred in two cases (one intraprocedural and one postprocedural stroke), and the MAE rate was 1.4%. The non-MAE rate was 98.6% according to Kaplan-Meier analysis, which was superior to the previously set performance goal. The deployment success, target lesion revascularization (TLR), in-stent restenosis, and cerebrovascular event rates were 99.3%, 2.4%, 8.5%, and 7.2%, respectively. The MAE rate in patients with normal CEA risk was 1.2%, which was similar to the high-risk CEA group, with no significant difference due to the small number of MAEs. CONCLUSIONS: The MAE rate following use of the CASPER stent was low (1.4%). The MAE, deployment success, TLR, in-stenosis, and cerebrovascular event rates were similar to those of previous reports.

Efficacy of Monitoring for Multiple Antiplatelet Therapy during Intracranial Stent Placement: A Preliminary Study.

Objective: During cerebral aneurysm embolization using intracranial stents, platelet aggregation increases owing to increased wall shear stress and a loss of vascular endothelial function at the stent implantation site. Preoperative multiple antiplatelet therapy was introduced to prevent severe thromboembolic complications due to increased platelet aggregation. However, specific guidelines for the administration and pharmacological evaluation of this therapy do not exist currently. We examined the benefits of perioperative platelet aggregation monitoring in a cohort of patients. Methods: We had 377 patients with unruptured intracranial aneurysms who underwent stent-assisted embolization at our hospital between December 2012 and November 2019. We ultimately included 181 patients in our final analysis. These patients were continuously administered aspirin (100 mg/day) and clopidogrel (75 mg/day) for more than 5 days before the procedure to the post-procedural period. Of these patients, 30 patients who underwent light transmission aggregometry (LTA) before procedure, post-procedure (3 days after procedure), and at first post-discharge clinic visit were included as the subjects. The following characteristics were studied: age; sex; presence/absence of hypertension, dyslipidemia, and/or diabetes mellitus; location of aneurysm; type/number of stent; technique for stent placement; duration of preoperative multiple antiplatelet therapy; perioperative platelet aggregation test results; and postoperative ischemic or hemorrhagic complications. Results: Among these 30 patients, the median duration of antiplatelet therapy prior to the preoperative platelet aggregation measurements was 7 (interquartile range [IQR]: 6-8) days, and post-discharge measurement of LTA was performed at a median period of 27 (IQR: 22-35.5) days after procedure. The preoperative, postoperative, and first post-discharge clinic visit LTA values for adenosine diphosphate (ADP)-induced platelet aggregation were 50% (IQR: 44-54%), 42.5% (IQR: 36-48%), and 36% (IQR: 32-40%), respectively. These results represented gradual decrease in LTA values and a significant difference between the preoperative and post-discharge values. The LTA values for collagen aggregation showed a significant difference evident between the preoperative and post-discharge values; preoperative 38% (IQR: 27-60%), postoperative 42% (IQR: 30-58%), post-discharge 28% (IQR: 20-42%), respectively. We had one thromboembolic complication and one hemorrhagic complication. The results indicated that appropriate platelet aggregation monitoring during multiple antiplatelet therapy prevents thromboembolic complications such as stent thrombosis. However, we also found that many patients demonstrated increased postoperative platelet aggregation inhibitory effects due to the postoperative continuation of the same multiple antiplatelet therapy that was used preoperatively. Conclusion: This study demonstrates that postoperative, continuous, oral antiplatelet therapy induces increased platelet aggregation inhibition effects, which may lead to hemorrhagic complications. Therefore, continued platelet aggregation monitoring after surgery may be important to allow for any necessary alterations to the therapeutic dose and regimen.

Delayed Complications Due to Polymer Coating Embolism after Endovascular Treatment.

There have recently been reports of patients who developed postprocedural symptoms or alterations due to delayed foreign body embolisms observed in imaging findings. Polymer coating of devices have been described as a possible cause of foreign body embolisms, manifesting in delayed granulomatous responses and exhibiting characteristic imaging findings. In four of 4,025 patients who underwent coil embolization in our hospital or its affiliated facilities, similar findings were observed. Delayed lesions appeared between 1 month and 1 year after the procedures. There was extensive edema in the perfusion area of the treated vessels. In two cases examined by contrast-enhanced magnetic resonance imaging, multiple solid enhancing lesions within vasogenic edema were observed. Biopsy revealed a membranous foreign body in a blood vessel with surrounding foreign body granuloma formation in 1 case. Because these findings are similar to those of cases reported previously, they were considered as a foreign body embolism due to coating separations from the devices. Polymer coating separation occurs most frequently from guidewires. Especially if a metal introducer is used, the risk of separation increases. Surgeons should carefully follow the manufacturers' instructions when they use these devices and should acknowledge and report any events that may occur. Although these complications are extremely rare, further studies are warranted of similar cases; and we should prepare and share information on these intravascular devices for wide-scale dissemination in the industry.

Histological and Transmission Electron Microscopy Results after Embolization with HydroSoft/HydroFrame Coils in Experimental Swine Aneurysm.

Coiling and clipping are standard treatment strategies for cerebral aneurysms. Regardless of the strategy used, recanalization may affect the patient's prognosis. The aim of this study was to histologically and morphologically compare the tissue proliferation after coil embolization using bare platinum coils versus second-generation hydrogel coils (HydroSoft/HydroFrame; MicroVention, Inc., Aliso Viejo, CA, USA). Endothelial-like cell proliferation was seen in both groups at 2 weeks after surgery. Macroscopic findings showed a tighter layer at 4 weeks in the hydrogel coil group, and histological and immunohistochemical findings revealed endothelial cell proliferation. This layer became much thicker and tighter at 4 weeks after surgery. Aneurysms treated with second-generation hydrogel coils may be more stable and have a lower incidence of recanalization than those treated with bare platinum coils because of the tight endothelial layer proliferation.

[Three Cases of Esophageal Submucosal Hematoma after Coiling for Unruptured Cerebral or Intracranial Aneurysms].

We report three cases of esophageal submucosal hematoma after treatment of unruptured intracranial aneurysms. All cases were in women with a mean age of 67.7 years. They were administered anti-platelet drugs before undergoing operations to deliver stents. All cases were administered general heparinization during the operation. All three cases developed sudden-onset hemoptysis or epigastric pain. The medical treatments included the temporary cessation or reduction of antiplatelet therapy and all cases were discharged with symptom cure and with the appearance of gastric intestinal fiber on computed tomography imaging. Esophageal submucosal hematoma has a good prognosis with medical therapy. We should consider the potential for esophageal submucosal hematoma after hemoptysis or epigastric pain after coiling of unruptured intracranial aneurysms that require antiplatelet or anticoagulant therapies.

Flow Diverter Therapy of a Giant Fusiform Vertebrobasilar Junction Aneurysm in a Child: Case Report.

The management of giant vertebrobasilar junction (VBJ) aneurysms is extremely challenging. Flow diverter (FD) therapy has become an important alternative to treat difficult intracranial aneurysms for both open surgery and conventional endovascular therapy. Herein, we report a rare case of a giant fusiform VBJ aneurysm in a child that is successfully treated with FD therapy.

Orbital Arteriovenous Fistula Coexistent with an Arteriovenous Hemangioma: A Rare Occurrence and Review of Literature.

BACKGROUND: Orbital arteriovenous fistula (AVF) is a rare entity with only 17 cases reported so far. An arteriovenous hemangioma is a distinct entity of an angioma that most frequently affects the skin. However, to our knowledge, there has not been a case arising in the orbit. CASE DESCRIPTION: A previously healthy, 73-year-old man had progressive proptosis for 1 month. At presentation, the patient showed considerable proptosis, hyperemia in the lower eyelid, chemosis, and total ophthalmoplegia on the right side. Computed tomography and magnetic resonance imaging revealed a round retro-orbital mass, 23 mm in maximal dimension, and lying in the inferomedial aspect of the orbit with an irregular-shaped lesion in the orbital apex. Cerebral angiography detected an orbital AVF fed by the ipsilateral maxillary and ophthalmic arteries and draining into the inferior ophthalmic vein. Stain of the retro-orbital mass was not identified. A transvenous coil embolization via the facial and superior ophthalmic veins achieved complete isolation of the AVF with satisfactory outcome. Two months later, the orbital mass, well circumscribed and lacking perilesional hemosiderin deposition, was microsurgically resected via a lateral orbitotomy. Histological diagnosis was consistent with an arteriovenous hemangioma. CONCLUSIONS: An AVF and arteriovenous hemangioma may simultaneously develop in the same orbit. In patients with symptomatic orbital AVF and coexisting other orbital pathology, strategies should be carefully planned before setting about the treatment.

Endovascular parent artery occlusion of proximal posterior cerebral artery aneurysms: a report of two cases.

We report two cases of proximal posterior cerebral artery (PCA) aneurysms treated with endovascular parent artery occlusion (PAO) with coils. In both cases, selective injection from the 4 F distal access catheter clearly showed the perforating arteries arising from the PCA. Case No 1, a 49-year-old woman, was successfully treated with preservation of a paramedian artery. Case No 2, a 54-year-old woman, was treated in the same manner. The patient underwent extensive thalamic infarction after the procedure because of paramedian artery occlusion. Endovascular PAO with coils is feasible for proximal PCA aneurysms; however, preservation of perforating arteries arising from the PCA is mandatory.

[Case Report of Cerebellar Vermis Arteriovenous Malformation Presenting with Hydrocephalus due to Aqueductal Stenosis].

A 56-year-old man complained of gait disturbance and confused thinking. Magnetic resonance imaging(MRI)revealed an arteriovenous malformation(AVM)of the cerebellar vermis(Spetzler-Martin grade IV)causing hydrocephalus. One dilated precentral cerebellar vein was compressing the aqueduct. After feeder embolization over 3 sessions using N-butyl cyanoacrylate(NBCA), the nidus was reduced to one-third in size. However, symptoms remained unimproved, and endoscopic third ventriculostomy(ETV)was performed. The third ventricle showed thinning of the floor, with a fenestration in part of the floor. Radiological findings and clinical symptoms improved, and the patient returned home after rehabilitation. The condition of the patient remained stable as of six months later. On angiography, the draining vein showed a pressure of 20 mmHg with no change in the residual AVM. Embolization alone achieved a reduction in nidus volume, but could not reduce venous pressure, and combination therapy including ETV proved necessary. Cases with hydrocephalus due to aqueductal stenosis by AVM are extremely rare. This pathology is discussed with reference to the literature.

Treatment results of endosaccular coil embolization of asymptomatic unruptured intracranial aneurysms in elderly patients.

BACKGROUND AND PURPOSE: We report the results of endosaccular coil embolization of asymptomatic unruptured intracranial aneurysms (UIAs) in elderly patients (≥65 years). MATERIALS: There were 375 elderly patients with 400 asymptomatic UIAs. Patients were divided into two groups: group A included patients aged 65-74 years and group B patients aged ≥75 years. RESULTS: Endovascular procedures were completed in 97.8% of patients. Immediate anatomical outcomes showed complete occlusion in 53.7%, residual neck in 18.9%, and residual aneurysm in 27.4%. Anatomical follow-ups (mean 36.3±28.1 months) were unchanged in 55.7%, improved in 22.6%, minor recurrence in 11.5%, and major recurrence in 10.2%. Procedure related complications occurred in 31 patients (8.3%). 15 patients had ischemic and 10 hemorrhagic complications. Retreatments were performed in 16 patients (4.3%). Among 366 patients technically completed, 363 (99.2%) showed a favorable clinical outcome (modified Rankin Scale (mRS) score <1) at 30 days. The remaining three patients showed a worsening of mRS >0 at 30 days. The latest clinical follow-up outcomes showed: mRS score 0 in 362 patients; mRS score 1 in one; mRS score 3 in one; mRS score 4 in one; and mRS score 5 in one patient. Permanent morbidity and mortality rates were 1.1% and 0%, respectively. There were no statistically significant differences in gender, comorbidities, aneurysm size, neck width, dome-to-neck ratio, immediate anatomical outcomes, anatomical follow-up outcomes, or procedure related complications between the groups. CONCLUSIONS: Endosaccular coil embolization is safe and feasible for elderly patients with asymptomatic UIAs. Old age itself should not be a contraindication.

Uncertainty in patients with unruptured intracranial aneurysms undergoing endovascular surgery: a qualitative and inductive study.

BACKGROUND: Advances in diagnostic imaging technology have increased opportunities to discover unruptured intracranial aneurysms (UIA), and prior research has shown that UIA patients experience uncertainty both when making choices regarding treatment and after surgery. OBJECTIVES: The purpose of this study was to clarify the nature of the uncertainty experienced by UIA patients who elect to undergo endovascular surgery. METHODS: Data from interviews with 31 subjects were synthesized with findings from previous research and then analyzed qualitatively and inductively. RESULTS: Six categories were derived from the analysis to describe the uncertainty experienced by UIA patients who undergo intravascular surgery: Nature of the Disease, Treatment Characteristics, Information, Decision-making, Course of the Future, and Living with UIA. DISCUSSION: The Treatment Characteristics and Decision-making categories reflect new aspects of uncertainty arising from advances in diagnostic imaging and appeared specific to patients with UIA. This suggests a need to select appropriate nursing methods adapted to the situation of each patient that can both reduce and manage their uncertainty. Developing an uncertainty scale for UIA patients based on the structural concepts clarified in this study and investigating reliability and validity of scores are topics for future research.

Adrenomedullin deficiency and aging exacerbate ischemic white matter injury after prolonged cerebral hypoperfusion in mice.

Adrenomedullin was originally isolated from pheochromocytoma cells and reduces insulin resistance by decreasing oxidative stress. White matter lesions induced by aging and hyperglycemia play a crucial role in cognitive impairment in poststroke patients. Here, we examine whether adrenomedullin deficiency and aging exacerbate ischemic white matter injury after prolonged cerebral hypoperfusion. Adrenomedullin heterozygous, wild-type young/aged mice were subjected to prolonged hypoperfusion. Prolonged cerebral hypoperfusion followed by immunohistochemical analysis was used to evaluate white matter injury. After prolonged hypoperfusion, white matter damage progressed in a time-dependent manner in AM(+/-) group compared with the wild-type group. The number of oligodendrocyte progenitor cells gradually increased after prolonged hypoperfusion, whereas oligodendrocytes decreased following a transient increase, but the ratio of increase was mild in the AM(+/-) group (P < 0.05). Oxidative stress was detected in oligodendrocytes, with a larger increase in the AM(+/-) group (P < 0.05). Aged mice showed the same tendency, but white matter damage was worse, especially in the aged AM(+/-) group. Our results demonstrated that white matter injury was increased in adrenomedullin deficiency, which induced oxidative stress. White matter injury was more exacerbated because of hyperglycemia in aged AM(+/-) group. Adrenomedullin may be an important target in the control of ischemic white matter injury.

[Systematic review of complications for proper informed consent: (10) endovascular therapy for unruptured intracranial aneurysms].

Less invasive neuroimaging modalities have recently resulted in the more frequent detection of unruptured intracranial aneurysms(UIAs). Therefore, more patients, than ever before, with UIAs are currently being referred to neurosurgeons, who then must inform their patients of the optimal management possibilities. Endovascular therapy has become an important and well-known alternative to surgical clipping. However, as many neurosurgeons are not yet familiar enough with endovascular therapy, it is difficult for them to clearly explain the risks to their patients. The purpose of this systematic review is to disclose the risks of endovascular therapy for UIAs, which should be helpful to neurosurgeons, so that they can provide the appropriate information to their patients in order to obtain informed consent. In the present study, the overall morbidity and mortality rate of endovascular therapy of UIAs was 4.4% and 0.7%, respectively. Elderly patients had a higher risk of morbidity and mortality than did younger patients. The average risks of thromboembolic events and intraprocedural aneurysm rupture were 6.6% and 1.7%, respectively. Although posttreatment bleeding was extremely rare, patients with incompletely occluded large UIAs were more at risk. Furthermore, large UIAs more frequently required retreatment than did smaller ones. Other complications(e.g., puncture site complications, side effects due to the contrast medium, radiation injuries, heparin-induced thrombocytopenia, perianeurysmal edema, hydrocephalus, and aseptic meningitis)must also be explained to the patient.

Differences in phosphodiesterase 3A and 3B expression after ischemic insult.

Phosphodiesterase (PDE) exists in the cardiovascular system, adipose tissue and platelets, and its inhibition increases the cellular levels of cAMP, which could activate cAMP-responsive element binding protein (pCREB). The present study was designed to map the expression of PDE3A/B in the forebrain and define the time course of PDE3 expression in the ischemic boundary zone after ischemia. The number of PDE3A-positive cells (neurons and endothelial cells) remained unchanged, while PDE3B-positive cells gradually increased after ischemia/reperfusion. In the corpus callosum, PDE3B was expressed in oligodendrocytes, oligodendrocyte progenitor cells, and astrocytes. PDE3B-expressing astrocytes showed gradual increase after ischemia/reperfusion. In the cortex, the majority of PDE3B-expressing cells before ischemia were neurons, though few were astrocytes. Ischemic insult resulted in gradual increase in PDE3B-expressing astrocytes and neurons, with larger increase in astrocytes. Expression of brain derived neurotrophic factor (BDNF) and B-cell leukemia/lymphoma 2 protein (Bcl-2) was detected in pCREB-positive cells, not in PDE3B-positive cells. Our results demonstrated that ischemic insult increased PDE3B expression, but not PDE3A, and changed the number and type of cells in a time-dependent manner. The variation of PDE3B-expression in the brain might play a crucial pathophysiological role, and regulation of PDE3B production might protect against ischemic brain damage.