Association of impaired neuronal migration with cognitive deficits in extremely preterm infants.

نویسندگان

  • Ken-Ichiro Kubo
  • Kimiko Deguchi
  • Taku Nagai
  • Yukiko Ito
  • Keitaro Yoshida
  • Toshihiro Endo
  • Seico Benner
  • Wei Shan
  • Ayako Kitazawa
  • Michihiko Aramaki
  • Kazuhiro Ishii
  • Minkyung Shin
  • Yuki Matsunaga
  • Kanehiro Hayashi
  • Masaki Kakeyama
  • Chiharu Tohyama
  • Kenji F Tanaka
  • Kohichi Tanaka
  • Sachio Takashima
  • Masahiro Nakayama
  • Masayuki Itoh
  • Yukio Hirata
  • Barbara Antalffy
  • Dawna D Armstrong
  • Kiyofumi Yamada
  • Ken Inoue
  • Kazunori Nakajima
چکیده

Many extremely preterm infants (born before 28 gestational weeks [GWs]) develop cognitive impairment in later life, although the underlying pathogenesis is not yet completely understood. Our examinations of the developing human neocortex confirmed that neuronal migration continues beyond 23 GWs, the gestational week at which extremely preterm infants have live births. We observed larger numbers of ectopic neurons in the white matter of the neocortex in human extremely preterm infants with brain injury and hypothesized that altered neuronal migration may be associated with cognitive impairment in later life. To confirm whether preterm brain injury affects neuronal migration, we produced brain damage in mouse embryos by occluding the maternal uterine arteries. The mice showed delayed neuronal migration, ectopic neurons in the white matter, altered neuronal alignment, and abnormal corticocortical axonal wiring. Similar to human extremely preterm infants with brain injury, the surviving mice exhibited cognitive deficits. Activation of the affected medial prefrontal cortices of the surviving mice improved working memory deficits, indicating that decreased neuronal activity caused the cognitive deficits. These findings suggest that altered neuronal migration altered by brain injury might contribute to the subsequent development of cognitive impairment in extremely preterm infants.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Cognitive outcome varies in adolescents born preterm, depending on gestational age, intrauterine growth and neonatal complications

AIM The aim of this study was to investigate long-term cognitive outcome in a cohort of 18-year-olds born preterm and previously assessed at the age of 5.5. METHODS We tested 134 adolescents born preterm with a very low birthweight of <1500 g and 94 term-born controls with a comprehensive cognitive battery at 18 years of age. The cohort was subdivided into 73 extremely preterm, 42 very preter...

متن کامل

Postnatal Erythropoietin Mitigates Impaired Cerebral Cortical Development Following Subplate Loss from Prenatal Hypoxia-Ischemia.

Preterm birth impacts brain development and leads to chronic deficits including cognitive delay, behavioral problems, and epilepsy. Premature loss of the subplate, a transient subcortical layer that guides development of the cerebral cortex and axonal refinement, has been implicated in these neurological disorders. Subplate neurons influence postnatal upregulation of the potassium chloride co-t...

متن کامل

Recent advancements in diffusion MRI for investigating cortical development after preterm birth—potential and pitfalls

Preterm infants are born during a critical period of brain maturation, in which even subtle events can result in substantial behavioral, motor and cognitive deficits, as well as psychiatric diseases. Recent evidence shows that the main source for these devastating disabilities is not necessarily white matter (WM) damage but could also be disruptions of cortical microstructure. Animal studies sh...

متن کامل

Extreme prematurity and attention deficit: epidemiology and prevention

EXTREME PREMATURITY AND ATTENTION IMPAIRMENT Preterm infants are at increased risk for a wide range of developmental disorders, including sensory, motor, cognitive, and other brain disorders (Lorenz et al., 1998; Bhutta et al., 2002; Aarnoudse-Moens et al., 2009), and the risk is highest for those infants born before 28 weeks gestation, i.e., extremely preterm or extremely low gestational age i...

متن کامل

Hypothyroxinemia in extremely low birth weight infants

Hypothyroxinemia of prematurity (HOP) is a transient alteration in thyroid hormone availabilityfound in more than half of extremely low birth weight infants (ELBW) born at less than 30 weeks [1]. HOP is characterized by very low total T4 (TT4) and free T4 (FT4) levels with a normal or low thyroid stimulating hormone (TSH); TT4 and FT4 show a nadir at 7-10 days of life and they may remained low ...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • JCI insight

دوره 2 10  شماره 

صفحات  -

تاریخ انتشار 2017