Limits...
Radiation-induced brain injury: A review.

Greene-Schloesser D, Robbins ME, Peiffer AM, Shaw EG, Wheeler KT, Chan MD - Front Oncol (2012)

Bottom Line: Irradiating pediatric and young adult rodent brains leads to several hippocampal changes including neuroinflammation and a marked reduction in neurogenesis.Studies using older rodents, that more closely match the adult human brain tumor population, indicate that, unlike pediatric and young adult rats, older rats fail to show a radiation-induced decrease in neurogenesis or a loss of mature neurons.Recently developed techniques in neuroscience and neuroimaging provide not only an opportunity to accomplish this, but they also offer the opportunity to identify new biomarkers and new targets for interventions to prevent or ameliorate these late effects.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, NC, USA.

ABSTRACT
Approximately 100,000 primary and metastatic brain tumor patients/year in the US survive long enough (>6 months) to experience radiation-induced brain injury. Prior to 1970, the human brain was thought to be highly radioresistant; the acute CNS syndrome occurs after single doses >30 Gy; white matter necrosis occurs at fractionated doses >60 Gy. Although white matter necrosis is uncommon with modern techniques, functional deficits, including progressive impairments in memory, attention, and executive function have become important, because they have profound effects on quality of life. Preclinical studies have provided valuable insights into the pathogenesis of radiation-induced cognitive impairment. Given its central role in memory and neurogenesis, the majority of these studies have focused on the hippocampus. Irradiating pediatric and young adult rodent brains leads to several hippocampal changes including neuroinflammation and a marked reduction in neurogenesis. These data have been interpreted to suggest that shielding the hippocampus will prevent clinical radiation-induced cognitive impairment. However, this interpretation may be overly simplistic. Studies using older rodents, that more closely match the adult human brain tumor population, indicate that, unlike pediatric and young adult rats, older rats fail to show a radiation-induced decrease in neurogenesis or a loss of mature neurons. Nevertheless, older rats still exhibit cognitive impairment. This occurs in the absence of demyelination and/or white matter necrosis similar to what is observed clinically, suggesting that more subtle molecular, cellular and/or microanatomic modifications are involved in this radiation-induced brain injury. Given that radiation-induced cognitive impairment likely reflects damage to both hippocampal- and non-hippocampal-dependent domains, there is a critical need to investigate the microanatomic and functional effects of radiation in various brain regions as well as their integration at clinically relevant doses and schedules. Recently developed techniques in neuroscience and neuroimaging provide not only an opportunity to accomplish this, but they also offer the opportunity to identify new biomarkers and new targets for interventions to prevent or ameliorate these late effects.

No MeSH data available.


Related in: MedlinePlus

Symptoms and timeline for the development of radiation-induced brain injury in patients treated with fWBI.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC3400082&req=5

Figure 1: Symptoms and timeline for the development of radiation-induced brain injury in patients treated with fWBI.

Mentions: Radiation-induced brain injury is often observed after fractionated partial or whole brain irradiation (fWBI); the syndrome includes both anatomic and functional deficits. Based on the time of clinical expression (Figure 1), radiation-induced brain injury is described in terms of acute, early delayed, and late delayed injury (Tofilon and Fike, 2000). Acute brain injury, expressed in days to weeks after irradiation, is rare with current radiation therapy techniques. Early delayed brain injury occurs 1–6 months post-irradiation and can involve transient demyelination with somnolence. Although both of these early injuries can result in severe reactions, they are normally reversible and resolve spontaneously. In contrast, late delayed brain injury, characterized histopathologically by vascular abnormalities, demyelination, and ultimately white matter necrosis (Schultheiss and Stephens, 1992), is usually observed >6 months post-irradiation; these late delayed injuries have been viewed as irreversible and progressive. Classically, late radiation-induced brain injury was viewed as due solely to a reduction in the proliferating capacity of glial (van den Maazen et al., 1993) or vascular endothelial (Calvo et al., 1988) cells. The loss of either of these cell types could ultimately produce white matter necrosis, but the loss of glial cells was thought to cause necrosis earlier than the loss of vascular endothelial cells. However, there is a growing awareness that patients receiving fWBI can have significant cognitive impairment at >6 months post-irradiation even when they do not have detectable anatomic abnormalities (Sundgren and Cao, 2009). The impact of cognitive impairment on a patient’s quality of life (QOL) is now recognized as second only to survival in clinical trials (Frost and Sloan, 2002).


Radiation-induced brain injury: A review.

Greene-Schloesser D, Robbins ME, Peiffer AM, Shaw EG, Wheeler KT, Chan MD - Front Oncol (2012)

Symptoms and timeline for the development of radiation-induced brain injury in patients treated with fWBI.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3400082&req=5

Figure 1: Symptoms and timeline for the development of radiation-induced brain injury in patients treated with fWBI.
Mentions: Radiation-induced brain injury is often observed after fractionated partial or whole brain irradiation (fWBI); the syndrome includes both anatomic and functional deficits. Based on the time of clinical expression (Figure 1), radiation-induced brain injury is described in terms of acute, early delayed, and late delayed injury (Tofilon and Fike, 2000). Acute brain injury, expressed in days to weeks after irradiation, is rare with current radiation therapy techniques. Early delayed brain injury occurs 1–6 months post-irradiation and can involve transient demyelination with somnolence. Although both of these early injuries can result in severe reactions, they are normally reversible and resolve spontaneously. In contrast, late delayed brain injury, characterized histopathologically by vascular abnormalities, demyelination, and ultimately white matter necrosis (Schultheiss and Stephens, 1992), is usually observed >6 months post-irradiation; these late delayed injuries have been viewed as irreversible and progressive. Classically, late radiation-induced brain injury was viewed as due solely to a reduction in the proliferating capacity of glial (van den Maazen et al., 1993) or vascular endothelial (Calvo et al., 1988) cells. The loss of either of these cell types could ultimately produce white matter necrosis, but the loss of glial cells was thought to cause necrosis earlier than the loss of vascular endothelial cells. However, there is a growing awareness that patients receiving fWBI can have significant cognitive impairment at >6 months post-irradiation even when they do not have detectable anatomic abnormalities (Sundgren and Cao, 2009). The impact of cognitive impairment on a patient’s quality of life (QOL) is now recognized as second only to survival in clinical trials (Frost and Sloan, 2002).

Bottom Line: Irradiating pediatric and young adult rodent brains leads to several hippocampal changes including neuroinflammation and a marked reduction in neurogenesis.Studies using older rodents, that more closely match the adult human brain tumor population, indicate that, unlike pediatric and young adult rats, older rats fail to show a radiation-induced decrease in neurogenesis or a loss of mature neurons.Recently developed techniques in neuroscience and neuroimaging provide not only an opportunity to accomplish this, but they also offer the opportunity to identify new biomarkers and new targets for interventions to prevent or ameliorate these late effects.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, NC, USA.

ABSTRACT
Approximately 100,000 primary and metastatic brain tumor patients/year in the US survive long enough (>6 months) to experience radiation-induced brain injury. Prior to 1970, the human brain was thought to be highly radioresistant; the acute CNS syndrome occurs after single doses >30 Gy; white matter necrosis occurs at fractionated doses >60 Gy. Although white matter necrosis is uncommon with modern techniques, functional deficits, including progressive impairments in memory, attention, and executive function have become important, because they have profound effects on quality of life. Preclinical studies have provided valuable insights into the pathogenesis of radiation-induced cognitive impairment. Given its central role in memory and neurogenesis, the majority of these studies have focused on the hippocampus. Irradiating pediatric and young adult rodent brains leads to several hippocampal changes including neuroinflammation and a marked reduction in neurogenesis. These data have been interpreted to suggest that shielding the hippocampus will prevent clinical radiation-induced cognitive impairment. However, this interpretation may be overly simplistic. Studies using older rodents, that more closely match the adult human brain tumor population, indicate that, unlike pediatric and young adult rats, older rats fail to show a radiation-induced decrease in neurogenesis or a loss of mature neurons. Nevertheless, older rats still exhibit cognitive impairment. This occurs in the absence of demyelination and/or white matter necrosis similar to what is observed clinically, suggesting that more subtle molecular, cellular and/or microanatomic modifications are involved in this radiation-induced brain injury. Given that radiation-induced cognitive impairment likely reflects damage to both hippocampal- and non-hippocampal-dependent domains, there is a critical need to investigate the microanatomic and functional effects of radiation in various brain regions as well as their integration at clinically relevant doses and schedules. Recently developed techniques in neuroscience and neuroimaging provide not only an opportunity to accomplish this, but they also offer the opportunity to identify new biomarkers and new targets for interventions to prevent or ameliorate these late effects.

No MeSH data available.


Related in: MedlinePlus