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1.
Article in English | MEDLINE | ID: mdl-38395054

ABSTRACT

BACKGROUND: We analyzed clinical and radiographic outcomes in patients undergoing anterior lumbar interbody fusions (ALIFs) using a new biomimetic titanium fusion cage (Titan nanoLOCK interbody, Medtronic, Minneapolis, Minnesota, United States). This specialized cage employs precise nanotechnology to stimulate inherent biochemical and cellular osteogenic reactions to the implant, aiming to amplify the rate of fusion. To our knowledge, this is the only study to assess early clinical and radiographic results in ALIFs. METHODS: We conducted a retrospective review of data for patients who underwent single or multilevel ALIF using this implant between October 2016 and April 2021. Indications for treatment were spondylolisthesis, postlaminectomy syndrome, or spinal deformity. Clinical and radiographic outcome data for these patients were collected and assessed. RESULTS: A total of 84 patients were included. The mean clinical follow-up was 36.6 ± 14 months. At 6 months, solid fusion was seen in 97.6% of patients. At 12 months, solid fusion was seen in 98.8% of patients. Significant improvements were seen in patient-reported outcome measures (PROMs; visual analog scale and Oswestry Disability Index) at 6 and 12 months compared with the preoperative scores (p < 0.001). One patient required reoperation for broken pedicle screws 2 days after the ALIF. None of the patients required readmission within 90 days of surgery. No patients experienced an infection. CONCLUSIONS: ALIF using a new titanium interbody fusion implant with a biomimetic surface technology demonstrated high fusion rates (97.6%) as early as 6 months. There was significant improvement in PROMs at 6 and 12 months.

2.
BMJ Case Rep ; 16(8)2023 Aug 30.
Article in English | MEDLINE | ID: mdl-37648279

ABSTRACT

Necrobiotic xanthogranuloma is a condition that was first identified in 1980 based on its characteristic histological identity, and it has been known since then as a dermatologic manifestation of an underlying systemic dysproteinemia. Intracranial manifestation is a rare presentation of this condition and has been reported only once in its more than 40 years of existence. Herein and to our knowledge, we report the second observation of an intracranial manifestation and, surprisingly, the first case without the expected dermatologic and systemic dysproteinemia associations. This case identifies an existing knowledge gap in our understanding of necrobiotic xanthogranuloma and emphasises the need for further research into understanding the presentation, comorbidities and management of this condition.


Subject(s)
Necrobiotic Xanthogranuloma , Humans , Necrobiotic Xanthogranuloma/complications , Necrobiotic Xanthogranuloma/diagnosis
3.
J Neurointerv Surg ; 15(3): 209-213, 2023 Mar.
Article in English | MEDLINE | ID: mdl-35232752

ABSTRACT

BACKGROUND: Few studies have explored the association between stroke thrombectomy (ST) volume and hospital accreditation with clinical outcomes. OBJECTIVE: To assess the association of ST case volume and accreditation status with in-hospital mortality and home discharge disposition using the national Medicare Provider Analysis and Review (MEDPAR) database. METHODS: Rates of hospital mortality, home discharge disposition, and hospital stay were compared between accredited and non-accredited hospitals using 2017-2018 MEDPAR data. The association of annual ST case volume with mortality and home disposition was determined using Pearson's correlation. Median rate of mortality and number of ST cases at hospitals within the central quartiles were estimated. RESULTS: A total of 29 355 cases were performed over 2 years at 847 US centers. Of these, 354 were accredited. There were no significant differences between accredited and non-accredited centers for hospital mortality (14.8% vs 14.5%, p=0.34) and home discharge (12.1% vs 12.0%, p=0.78). A significant positive correlation was observed between thrombectomy volume and home discharge (r=0.88; 95% CI 0.58 to 0.97, p=0.001). A significant negative relationship was found between thrombectomy volume and mortality (r=-0.86; 95% CI -0.97 to -0.49, p=0.002). Within the central quartiles, the median number of ST cases at hospitals with mortality was 24/year, and the median number of ST cases at hospitals with home discharge rate was 23/year. CONCLUSION: A higher volume of ST cases was associated with lower mortality and higher home discharge rate. No significant differences in mortality and discharge disposition were found between accredited and non-accredited hospitals.


Subject(s)
Hospital Mortality , Patient Discharge , Stroke , Thrombectomy , Aged , Humans , Accreditation , Hospitals , Medicare , Stroke/surgery , United States/epidemiology
4.
Oper Neurosurg (Hagerstown) ; 24(1): 11-16, 2023 01 01.
Article in English | MEDLINE | ID: mdl-36251417

ABSTRACT

BACKGROUND: The use of modern transfemoral balloon guide catheters (BGC) for flow reversal during carotid artery stenting is scarcely described in the literature but represents a promising and efficient technique for embolic protection. OBJECTIVE: To describe a flow-reversal technique using the Walrus BGC (Q'Apel Medical Inc.) and report our center's experience. METHODS: We performed a retrospective analysis of data for consecutive patients aged 18 years or older who underwent elective carotid artery stenting with the use of flow reversal through the Walrus BGC between July 2020 and September 2021. Patient characteristics, procedural details, and clinical follow-up were evaluated. RESULTS: One hundred and five patients were included. Mean age was 69.8 ± 9.4 years, and 36 (34.3%) were women. The most common comorbidities were hyperlipidemia (76.2%) and hypertension (57.1%). Fifty-nine (56.2%) patients were symptomatic. Ninety-nine (94.3%) patients had stenosis ≥70%. Contralateral stenosis ≥50% was present in 44 patients (41.9%). Distal filters were used after flow reversal was established in 90 patients (85.7%). Angioplasty was performed in 85 patients (80.9%). Stenting was successful in 100% of cases. No periprocedural transient ischemic attacks (TIAs) or strokes occurred. Stroke occurred in 2 patients (1.9%) during the 30-day follow-up period, resulting in 1 (0.9%) death. CONCLUSION: In our experience, this technique was safe, feasible, and efficient, with 100% technical success and no periprocedural thromboembolic complications. More extensive studies are needed to establish the role of proximal protection with flow reversal using modern BGCs.


Subject(s)
Carotid Stenosis , Stroke , Female , Animals , Male , Stents , Carotid Stenosis/surgery , Carotid Stenosis/complications , Walruses , Retrospective Studies , Constriction, Pathologic/complications , Stroke/surgery , Carotid Arteries , Catheters
5.
BMJ Case Rep ; 15(4)2022 Apr 29.
Article in English | MEDLINE | ID: mdl-35487628

ABSTRACT

Gallium 68 (68Ga) 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid labelled octreotate ([68Ga]Ga-DOTA-TATE) positron emission tomography (PET) is an established imaging technique for identifying tumours of neuroendocrine origin and meningiomas; the radiotracer binds to somatostatin receptor type 2 (SSTR2), which is richly expressed by these malignancies. Here, we present a rare case hinting at novel ischaemic stroke detection by [68Ga]Ga-DOTA-TATE PET scan. The scan was performed 14 days post resection of an atypical meningioma with the intention to assess the extent of residual tumour for radiosurgical treatment of the operative cavity. Surprisingly, the [68Ga]Ga-DOTA-TATE PET-avid region corresponded to an area of perioperative subacute ischaemic stroke detected by MRI. This case corroborates the two previously reported cases of incidental detection of ischaemic stroke during routine [68Ga]Ga-DOTA-TATE PET imaging, collectively suggesting the need for caution when interpreting the imaging findings. A possible underlying mechanism for [68Ga]Ga-DOTA-TATE uptake in stroke is increased SSTR2 expression by macrophages recruited into infarcted tissue.


Subject(s)
Brain Ischemia , Ischemic Stroke , Meningeal Neoplasms , Meningioma , Radiosurgery , Stroke , Craniotomy , Gallium Radioisotopes , Heterocyclic Compounds, 1-Ring , Humans , Meningeal Neoplasms/diagnostic imaging , Meningeal Neoplasms/surgery , Meningioma/diagnostic imaging , Meningioma/surgery , Radiopharmaceuticals , Stroke/diagnostic imaging , Stroke/etiology , Tomography, X-Ray Computed/methods
6.
World Neurosurg ; 152: e144-e148, 2021 08.
Article in English | MEDLINE | ID: mdl-34033957

ABSTRACT

BACKGROUND: The use of balloon guide catheters (BGCs) for proximal flow arrest during neurointerventional procedures has been limited owing to the incompatibility of BGCs with large-bore aspiration catheters and difficulty in device navigation. The objective of our study was to describe the use of the Walrus catheter (Q'Apel Medical, Fremont, California, USA), a new 8F BGC, with a variety of aspiration catheters and procedures requiring flow arrest. METHODS: Consecutive cases using Walrus BGCs for proximal flow arrest during mechanical thrombectomy for acute stroke cases were recorded. The procedure indication, vessel occlusion site, technique, first-pass effect (modified thrombolysis in cerebral infarction score of 2C or 3 after the first recanalization attempt), and complications were recorded and evaluated statistically. RESULTS: Our study included 57 patients who had undergone mechanical thrombectomy. In addition to mechanical thrombectomy, the Walrus BGC was used in conjunction with the following techniques: stent retrieval in 2 patients (3.5%), stent retrieval followed by aspiration (Solumbra technique) in 41 (71.9%), and aspiration followed by stent retrieval in 14 patients (24.6%). Eight different aspiration catheters were used in 56 of these 57 procedures. The first-pass effect (modified thrombolysis in cerebral infarction score of 2C and 3) was achieved in 36 (63.2%) of 57 procedures. Two patients (3.5%) had experienced intraoperative complications (symptomatic intracerebral hemorrhage) and one patient (1.8%) had died in-hospital. CONCLUSIONS: Our results have demonstrated that the Walrus BGC is a highly navigable 8F guide catheter compatible with most available aspiration catheters. Owing to its compatibility with most available aspiration catheters and ease of use, the Walrus BGC is a valuable addition to the tools available for mechanical thrombectomy.


Subject(s)
Balloon Embolectomy/methods , Brain Ischemia/surgery , Mechanical Thrombolysis/methods , Stroke/surgery , Aged , Aged, 80 and over , Balloon Embolectomy/instrumentation , Brain Ischemia/diagnosis , Female , Humans , Male , Mechanical Thrombolysis/instrumentation , Middle Aged , Retrospective Studies , Stroke/diagnosis , Treatment Outcome
7.
Interv Neuroradiol ; 27(4): 566-570, 2021 Aug.
Article in English | MEDLINE | ID: mdl-33356726

ABSTRACT

BACKGROUND: Radial loops are rare congenital radial artery anomalies that may pose a significant challenge to successful transradial neuroangiography. In this case series, we describe the anatomy and frequency of radial artery loops and provide a technique for successful navigation of this anatomic anomaly. METHODS: We reviewed our database of radial diagnostic or interventional neuroangiographic procedures to identify cases in which a radial loop was encountered during the procedure. The loop pattern, the presence of an associated recurrent radial artery branch, navigation technique, and procedure-related complications were recorded. A descriptive analysis was performed. RESULTS: A total of 997 transradial approach procedures were performed over a 9-month period. A radial loop was identified in 10 (1.0%) patients. The average age was 68.6 ± 14.3 years. A microcatheter advanced over a microwire was used to navigate the loop and avoid entry into the recurrent branch. A diagnostic neuroangiographic procedure was performed successfully in 8 cases and an intervention was performed successfully in 1 case. A 360° loop was present in 2 of these cases. In each case, transradial access was performed successfully. In 1 other diagnostic case, transradial access was aborted, and the femoral artery was accessed to perform the procedure. CONCLUSIONS: A radial loop was present in 1% of the cases in this series. Our technical results suggest that this anomaly should not be considered a contraindication to transradial neuroangiography because the procedure was successfully performed in most (9 of 10) cases using a microcatheter system to navigate the loop.


Subject(s)
Endovascular Procedures , Radial Artery , Aged , Aged, 80 and over , Femoral Artery , Humans , Middle Aged , Radial Artery/diagnostic imaging , Radial Artery/surgery
8.
World Neurosurg ; 146: e6-e13, 2021 02.
Article in English | MEDLINE | ID: mdl-32956893

ABSTRACT

BACKGROUND: Lumbar spine fusion surgery is traditionally performed with rigid fixation. Because the rigidity is often supraphysiologic, semirigid rods were developed. To the best of our knowledge, a comprehensive evaluation of rod material type on surgical outcomes has yet to be conducted. METHODS: A systematic review based on PRISMA guidelines was conducted across 3 electronic databases. After examination for inclusion and exclusion criteria, data were extracted from the studies. RESULTS: Seventeen studies, including 1399 patients, were included in this review. The mean rigid rod fusion rate is 92.2% and 95.5% for semirigid rods (P = 0.129). The mean improvement in back pain was 60.6% in rigid rods and 71.6% in semirigid rods. The improvement in leg pain was 81.9% and 77.2%, respectively. There were no differences in visual analog scale back pain score (P = 0.098), visual analog scale leg pain score (P = 0.136), or in functional improvement between rigid and semirigid rods (P = 0.143). There was no difference (P = 0.209) in the reoperation rate between rigid rods (13.1%) and semirigid rods (6.5%). There was a comparable incidence of adjacent segment disease (3%), screw fracture (1.7%), and wound infection (1.9%) between rod material types. CONCLUSIONS: There is a moderate level of evidence supporting that surgical intervention results in high fusion rates regardless of rod material type. Surgical intervention improves back pain, leg pain, and function, with neither material type showing clear superiority. There are comparable rates of reoperation, development of adjacent segment disease, development of mechanical complications, and incidence of infection in both rigid and semirigid rods. Further studies regarding rod material type are warranted.


Subject(s)
Back Pain/surgery , Bone Screws , Lumbar Vertebrae/surgery , Spinal Fusion , Bone Screws/adverse effects , Humans , Polyethylene Glycols/therapeutic use , Spinal Fusion/methods , Treatment Outcome
9.
J Neurointerv Surg ; 13(2): 109-113, 2021 Feb.
Article in English | MEDLINE | ID: mdl-32690759

ABSTRACT

BACKGROUND: Radial access has become popular among neurointerventionalists because it has favorable risk profiles compared with femoral access. Difficulties in accessing or navigating the radial artery have been viewed as a reason to convert to femoral access, but ulnar artery access may prevent complications associated with transfemoral procedures. OBJECTIVE: To evaluate the safety and feasibility of ulnar access for neurointerventions and diagnostic neuroangiographic procedures. METHODS: Consecutive patients who underwent diagnostic angiography or neurointerventional procedures via ulnar access between July 1, 2019 and April 15, 2020 were included. Data recorded were demographics, procedure indication, devices, technique, and complications. Descriptive analysis was performed. RESULTS: Ulnar artery access was obtained for 21 procedures in 18 patients (mean age 70.3±7.8 years; nine men). Procedures included 13 diagnostic angiograms and eight neurointerventions (3 left middle meningeal artery embolization, 1 of which was aborted; 2 carotid artery stenting; 2 angioplasty; 1 mechanical thrombectomy for in-stent thrombosis). A right-sided approach with ultrasound guidance was used for all cases except one. Indications included small caliber radial artery (n=9), radial artery occlusion (n=10), and radial artery preservation for potential bypass (n=2). A 5-French slender sheath was used for diagnostic angiography; a 6-French slender sheath was used for neurointerventions. No case required conversion to femoral access. Two patients had minor hematomas after the procedure; one other had ulnar artery occlusion on 30-day ultrasonography. CONCLUSION: Ulnar access is safe and feasible for diagnostic and interventional neuroangiographic procedures. It provides a useful alternative to radial access, potentially avoiding complications associated with femoral access.


Subject(s)
Angioplasty/methods , Arterial Occlusive Diseases/diagnostic imaging , Arterial Occlusive Diseases/therapy , Cerebral Angiography/methods , Embolization, Therapeutic/methods , Ulnar Artery/diagnostic imaging , Aged , Aged, 80 and over , Angioplasty/adverse effects , Cerebral Angiography/adverse effects , Embolization, Therapeutic/adverse effects , Feasibility Studies , Female , Humans , Male , Middle Aged , Retrospective Studies , Stents/adverse effects
10.
Dev Psychobiol ; 62(2): 170-180, 2020 03.
Article in English | MEDLINE | ID: mdl-31456229

ABSTRACT

Methylphenidate (MP) is a commonly prescribed psychostimulant to individuals with Attention Deficit Hyperactivity Disorder, and is often used illicitly among healthy individuals with intermittent breaks to coincide with breaks from school. This study examined how intermittent abstinence periods impact the physiological and behavioral effects of chronic oral MP self-administration in rats, and whether these effects persist following prolonged abstinence from the drug. Rats were treated orally with water, low-dose (LD), or high-dose (HD) MP, beginning at PND 28. This daily access continued for three consecutive weeks followed by a 1-week abstinence; after three repeats of this cycle, there was a 5-week abstinence period. Throughout the study, we examined body weight, food intake, locomotor activity, and anxiety- and depressive-like behaviors. During the treatment phase, HD MP decreased body weight, food intake, and depressive- and anxiety-like behaviors, while it increased locomotor activity. During intermittent abstinence, the effects of MP on locomotor activity were eliminated. During prolonged abstinence, most of the effects of HD MP were ameliorated to control levels, with the exception of weight loss and anxiolytic effects. These findings suggest that intermittent exposure to chronic MP causes physiological and behavioral effects that are mostly reversible following prolonged abstinence.


Subject(s)
Behavior, Animal/drug effects , Body Weight/drug effects , Central Nervous System Stimulants/pharmacology , Eating/drug effects , Locomotion/drug effects , Methylphenidate/pharmacology , Animals , Attention Deficit Disorder with Hyperactivity/drug therapy , Central Nervous System Stimulants/administration & dosage , Disease Models, Animal , Male , Methylphenidate/administration & dosage , Rats , Rats, Sprague-Dawley
11.
Behav Brain Res ; 356: 189-196, 2019 01 01.
Article in English | MEDLINE | ID: mdl-30149034

ABSTRACT

Methylphenidate (MP) is a commonly prescribed psychostimulant for Attention Deficit Hyperactivity Disorder (ADHD). We recently reported behavioral and developmental effects of chronic MP use in healthy rats. The current study investigated how interrupting chronic MP treatment with weekend abstinence altered the behavioral and physiological consequences of chronic MP treatment, and if prolonged abstinence would reverse the observed effects. Male Sprague Dawley rats were assigned to one of three treatment groups: water (W); low dose (LD) MP; and high dose (HD) MP. For 13 weeks, rats had access to drink from a bottle containing 4 mg/kg MP (LD), 30 mg/kg MP (HD) or water (W) for 1 h, and 10 mg/kg MP (LD), 60 mg/kg MP (HD) or water (W) for the next 7 h, each week day. During weekends, all animals received only water as well as throughout the 5-week-long abstinence phase, which immediately followed the treatment phase. Throughout the treatment phase, regardless of weekend abstinence, chronic MP resulted in significant decreased food and fluid intake and body weight. Also, HD MP exposure resulted in the following behavioral effects: increased open field and circadian locomotor activity; increased latency to immobility and decreased time spent immobile in the forced swim test; increased center activity in the open field and percent of time spent in an open arm of the elevated-plus-maze; and increased social affiliation and memory in the Crawley's three chamber sociability test. During the prolonged (5-week) abstinence phase, all these effects were reversed while HD treated rats increased their fluid intake. These results indicated that intermittent brief abstinence periods (weekend's off-treatment) produced the same behavioral and developmental effects as those previously reported with chronic (7 days/week) MP treatment, but were reversible following a prolonged abstinence period (5 weeks).


Subject(s)
Attention Deficit Disorder with Hyperactivity/drug therapy , Methylphenidate/administration & dosage , Methylphenidate/pharmacology , Administration, Oral , Animals , Behavior, Animal/drug effects , Central Nervous System Stimulants/pharmacology , Dose-Response Relationship, Drug , Locomotion/drug effects , Male , Maze Learning/drug effects , Motor Activity/drug effects , Rats , Rats, Sprague-Dawley , Self Administration
12.
Pharmacol Biochem Behav ; 172: 22-32, 2018 09.
Article in English | MEDLINE | ID: mdl-30030127

ABSTRACT

Chronic oral methylphenidate (MP) exposure in rats is associated with numerous developmental and behavioral consequences. The present study investigated the persistence of the effects of chronic oral MP exposure after abstinence from MP use. Male and female rats were exposed to daily orally self-administered water, low dose MP (LD), or high dose (HD) MP for 13 weeks, followed by a 4-week abstinence period. Fluid, food consumption and bodyweights were monitored and animals were tested for locomotor activity, anxiety- and depressive-like symptoms, learning and memory, and social behavior during both the treatment and abstinence phases of the experiment. During treatment, MP attenuated bodyweight regardless of sex, but increased food and fluid consumption in females and males by 20.7% and 30.1%, respectively. MP also increased locomotor activity in both males and females observed as increased distance travelled in an open field. (59.1% and 95.9%, respectively) and increased locomotor activity in the home cage over a 24-hour circadian cycle (45.5% and 63.0%). Additionally, MP exerted an anxiolytic effect observed as increased time spent in the open arms of an elevated plus maze (31.1% in HD males, 59.2% in HD females), and an increased latency to immobility in a forced swim test (330% in HD males, 418% in HD females). The effects of MP (bodyweight, consumption, locomotion, anxiolytic, and anti-depressive) were, almost without exception, eliminated during the abstinence period. MP had no impact on learning and memory performance as measured by a T-maze, or social behavior during treatment. These findings suggest that the behavioral consequences of chronic oral MP treatment in our preclinical model are reversible in rats following an abstinence period from use of the drug.


Subject(s)
Central Nervous System Stimulants/pharmacology , Methylphenidate/pharmacology , Substance Withdrawal Syndrome , Administration, Oral , Animals , Central Nervous System Stimulants/chemistry , Female , Male , Methylphenidate/administration & dosage , Rats , Rats, Sprague-Dawley
13.
Dev Psychobiol ; 60(4): 380-394, 2018 05.
Article in English | MEDLINE | ID: mdl-29442358

ABSTRACT

This study investigated the effect of maternal care on adolescent ethanol consumption, sensitivity to ethanol-induced hypnosis, as well as gonadal hormones and γ-aminobutyric acid type-A (GABAA ) systems. Long Evans rat dams were categorized by maternal licking/grooming (LG) frequency into High- and Low-LG mothers. Both female and male offspring from Low-LG rats demonstrated a greater sensitivity to ethanol-induced hypnosis in the loss-of-righting-reflex test at ethanol doses of 3.0 and 3.5 g/kg during late-adolescence (postnatal Day 50) but not at mid-adolescence (postnatal Day 42). However, we found no effect of maternal care on consumption of a 5% ethanol solution in a two-bottle choice test. We further investigated the association between the observed variations in sensitivity to ethanol-induced hypnosis and baseline hormonal levels in males. In male offspring from Low-LG mothers compared to High-LG mothers, baseline plasma corticosterone and progesterone levels were higher. GABAA α1 and δ subunit expressions were also higher in the cerebral cortex of Low-LG males but lower in the cerebellar synaptosomal fraction. Early environmental influences on adolescent sensitivity to ethanol-induced hypnosis, consumption, and preference may be mediated by gonadal hormones and possibly through GABAergic functions.


Subject(s)
Brain/metabolism , Central Nervous System Depressants/pharmacology , Corticosterone/blood , Ethanol/pharmacology , Immobility Response, Tonic/drug effects , Maternal Behavior/physiology , Progesterone/blood , Receptors, GABA-A/metabolism , Animals , Central Nervous System Depressants/administration & dosage , Ethanol/administration & dosage , Female , Male , Rats , Rats, Long-Evans
14.
Alcohol ; 60: 191-199, 2017 05.
Article in English | MEDLINE | ID: mdl-28433421

ABSTRACT

Behavioral consequences of prenatal alcohol exposure (PAE) can be transmitted from in utero-exposed F1 generation to their F2 offspring. This type of transmission is modulated by genetic and epigenetic mechanisms. This study investigated the intergenerational consequences of prenatal exposure to a low ethanol dose (1 g/kg) during gestational days 17-20, on ethanol-induced hypnosis in adolescent male F1 and F2 generations, in two strains of rats. Adolescent Long-Evans and Sprague-Dawley male rats were tested for sensitivity to ethanol-induced hypnosis at a 3.5-g/kg or 4.5-g/kg ethanol dose using the loss of righting reflex (LORR) paradigm. We hypothesized that PAE would attenuate sensitivity to ethanol-induced hypnosis in the ethanol-exposed animals in these two strains and in both generations. Interestingly, we only found this effect in Sprague-Dawley rats. Lastly, we investigated PAE related changes in expression of GABAA receptor α1, α4, and δ subunits in the cerebral cortex of the PAE sensitive Sprague-Dawley strain. We hypothesized a reduction in the cerebral cortex GABAA receptor subunits' expression in the F1 and F2 PAE groups compared to control animals. GABAA receptor α1, α4, and δ subunits protein expressions were quantified in the cerebral cortex of F1 and F2 male adolescents by western blotting. PAE did not alter cerebral cortical GABAA receptor subunit expressions in the F1 generation, but it decreased GABAA receptor α4 and δ subunits' expressions in the F2 generation, and had a tendency to decrease α1 subunit expression. We also found correlations between some of the subunits in both generations. These strain-dependent vulnerabilities to ethanol sensitivity, and intergenerational PAE-mediated changes in sensitivity to alcohol indicate that genetic and epigenetic factors interact to determine the outcomes of PAE animals and their offspring.


Subject(s)
Alcohol Drinking/adverse effects , Behavior, Animal/drug effects , Cerebral Cortex/drug effects , Ethanol/toxicity , Prenatal Exposure Delayed Effects , Receptors, GABA-A/drug effects , Age Factors , Alcohol Drinking/genetics , Alcohol Drinking/metabolism , Alcohol Drinking/psychology , Animals , Blood Alcohol Content , Cerebral Cortex/metabolism , Cerebral Cortex/pathology , Dose-Response Relationship, Drug , Epigenesis, Genetic/drug effects , Ethanol/blood , Female , Gestational Age , Male , Maternal Exposure , Pregnancy , Rats, Long-Evans , Rats, Sprague-Dawley , Reaction Time , Receptors, GABA-A/genetics , Receptors, GABA-A/metabolism , Reflex, Righting/drug effects , Species Specificity , Time Factors
15.
Alcohol Clin Exp Res ; 40(3): 497-506, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26876534

ABSTRACT

BACKGROUND: Prenatal alcohol exposure (PAE) enhances the risk for alcoholism by increasing the propensity to consume alcohol and altering neurophysiological response to alcohol challenge. Trans-generationally transmittable genetic alterations have been implicated in these behavioral changes. To date, transgenerational transmission of PAE-induced behavioral responses to alcohol has never been experimentally investigated. Therefore, we explored the transgenerational transmission of PAE-induced behavioral effects across 3 generations. METHODS: Pregnant Sprague Dawley dams received 1 g/kg ethanol (EtOH) or water daily on gestational days 17 through 20 via gavage, or remained untreated in their home cages. To produce second filial (F2) or F3 generations, similarly treated adult F1 or F2 offspring were mated and left undisturbed through gestation. On postnatal day (PND) 14, male and female F1, F2, and F3 offspring were tested for consumption of 5% (w/v) EtOH (in water), or water. Using the loss of righting reflex (LORR) paradigm on PND 42, F1 and F2 adolescent male offspring were tested for sensitivity to acute EtOH-induced sedation-hypnosis at 3.5 or 4.5 g/kg dose. F3 male adolescents were similarly tested at 3.5 g/kg dose. Blood EtOH concentration (BEC) was measured at waking. RESULTS: EtOH exposure increased EtOH consumption compared to both water and untreated control groups in all generations. EtOH-treated group F1 and F2 adolescents displayed attenuated LORR duration compared to the water group. No attenuated LORR was observed in the F3 generation. BEC at waking corroborated with the significant LORR duration differences while also revealing differences between untreated control and water groups in F1 and F2 generations. CONCLUSIONS: Our results provide novel behavioral evidence attesting that late gestational moderate EtOH exposure increases EtOH intake across 3 generations and may alter sensitivity to EtOH-induced sedation-hypnosis across 2 generations.


Subject(s)
Alcohol Drinking/psychology , Ethanol/administration & dosage , Ethanol/toxicity , Prenatal Exposure Delayed Effects/chemically induced , Prenatal Exposure Delayed Effects/psychology , Alcohol Drinking/genetics , Animals , Animals, Newborn , Female , Male , Pregnancy , Prenatal Exposure Delayed Effects/genetics , Rats , Rats, Sprague-Dawley
16.
Physiol Behav ; 148: 111-21, 2015 Sep 01.
Article in English | MEDLINE | ID: mdl-25575692

ABSTRACT

Gestational alcohol use is well documented as detrimental to both maternal and fetal health, producing an increase in offspring's tendency for alcoholism, as well as in behavioral and neuropsychological disorders. In both rodents and in humans, parental care can influence the development of offspring physiology and behavior. Animal studies that have investigated gestational alcohol use on parental care and/or their interaction mostly employ heavy alcohol use and single strains. This study aimed at investigating the effects of low gestational ethanol dose on parental behavior and its transgenerational transmission, with comparison between two rat strains. Pregnant Sprague Dawley (SD) and Long Evans (LE) progenitor dams (F0) received 1g/kg ethanol or water through gestational days 17-20 via gavage, or remained untreated in their home cages. At maturity, F1 female offspring were mated with males of the same strain and treatment and were left undisturbed through gestation. Maternal behavior was scored in both generations during the first six postnatal days. Arch-back nursing (ABN) was categorized as: 1, when the dam demonstrated minimal kyphosis; 2, when the dam demonstrated moderate kyphosis; and 3, when the dam displayed maximal kyphosis. Overall, SD showed greater amounts of ABN than LE dams and spent more time in contact with their pups. In the F0 generation, water and ethanol gavage increased ABN1 and contact with pups in SD, behaviors which decreased in treated LE. For ABN2, ethanol-treated SD dams showed more ABN2 than water-treated dams, with no effect of treatment on LE animals. In the F1 generation, prenatal exposure affected retrieval. Transgenerational transmission of LG was observed only in the untreated LE group. Strain-specific differences in maternal behavior were also observed. This study provides evidence that gestational gavage can influence maternal behavior in a strain-specific manner. Our results also suggest that the experimental procedure during gestation and genetic variations between strains may play an important role in the behavioral effects of prenatal manipulations.


Subject(s)
Central Nervous System Depressants/toxicity , Ethanol/toxicity , Maternal Behavior , Prenatal Exposure Delayed Effects/chemically induced , Alcohol Drinking/physiopathology , Analysis of Variance , Animals , Animals, Newborn , Female , Grooming , Male , Posture , Pregnancy , Prenatal Exposure Delayed Effects/nursing , Prenatal Exposure Delayed Effects/physiopathology , Rats , Rats, Long-Evans , Rats, Sprague-Dawley , Species Specificity , Time Factors
17.
Tokai J Exp Clin Med ; 38(2): 82-92, 2013 Jul 20.
Article in English | MEDLINE | ID: mdl-23868740

ABSTRACT

The use of anti-retroviral drugs during pregnancy has increased since the demonstration of reduction of mother-to-child transmission of HIV with highly active antiretroviral therapy (HAART). The risk of HAART cannot be ruled out; data are generally limited or varied. This study intends to thoroughly assess the teratogenic effect of HAART on the organogenesis stage of fetal development using animal model. Pregnant rats were divided into 13 groups with 12 animals per group. The therapeutic doses of drug administration were done to simulate the treatment pattern in APIN HIV/AIDS Clinic of the University of Lagos Teaching Hospital, Nigeria (find detailed treatment groups in methodology). Six rats in each group were randomly selected and sacrificed on day 20 by cervical dislocation prior to day 21 of gestation and the foetuses were harvested through abdominal incision for physical examination. Blood samples were collected from the 1st filial rats of the remaining six animals for biochemical and haematological examination. The liver, kidney, heart and brain of all the sacrificed animals were used for histopathological examination. There were significant (P ≤ 0.05) low birth weights of the foetuses of the animals that were treated with HAART. Results also revealed a reduction (P ≤ 0.05) in the platelets counts, WBC and RBC of most treatment groups at the first filial generation. Significant (P ≤ 0.05) elevations in the levels of AST and UA in the foetuses of the animals treated with HAART were also observed. It can be concluded that administration of single and combined antiretrovirals have potential teratogenic effect.


Subject(s)
Abnormalities, Drug-Induced/etiology , Antiretroviral Therapy, Highly Active/adverse effects , Congenital Abnormalities/etiology , Fetal Development/drug effects , Organogenesis/drug effects , Animals , Blood Cell Count , Female , Infant, Low Birth Weight , Male , Maternal-Fetal Exchange , Models, Animal , Pregnancy , Rats , Rats, Inbred Strains , Risk
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